Researchers have been looking for something that can help the body heal itself. Although studies are ongoing, stem cell research brings this notion of regenerative medicine a step closer. However, many of its ideas and concepts remain controversial. So, what are stem cells, and why are they so important?

Stem cells are cells that can develop into other types of cells. For example, they can become muscle or brain cells. They can also renew themselves by dividing, even after they have been inactive for a long time.

Stem cell research is helping scientists understand how an organism develops from a single cell and how healthy cells could be useful in replacing cells that are not working correctly in people and animals.

Researchers are now studying stem cells to see if they could help treat a variety of conditions that impact different body systems and parts.

This article looks at types of stem cells, their potential uses, and some ethical concerns about their use.

The human body requires many different types of cells to function, but it does not produce every cell type fully formed and ready to use.

Scientists call a stem cell an undifferentiated cell because it can become any cell. In contrast, a blood cell, for example, is a differentiated cell because it has already formed into a specific kind of cell.

The sections below look at some types of stem cells in more detail.

Scientists extract embryonic stem cells from unused embryos left over from in vitro fertilization procedures. They do this by taking the cells from the embryos at the blastocyst stage, which is the phase in development before the embryo implants in the uterus.

These cells are undifferentiated cells that divide and replicate. However, they are also able to differentiate into specific types of cells.

There are two main types of adult stem cells: those in developed bodily tissues and induced pluripotent stem (iPS) cells.

Developed bodily tissues such as organs, muscles, skin, and bone include some stem cells. These cells can typically become differentiated cells based on where they exist. For example, a brain stem cell can only become a brain cell.

On the other hand, scientists manipulate iPS cells to make them behave more like embryonic stem cells for use in regenerative medicine. After collecting the stem cells, scientists usually store them in liquid nitrogen for future use. However, researchers have not yet been able to turn these cells into any kind of bodily cell.

Scientists are researching how to use stem cells to regenerate or treat the human body.

The list of conditions that stem cell therapy could help treat may be endless. Among other things, it could include conditions such as Alzheimers disease, heart disease, diabetes, and rheumatoid arthritis. Doctors may also be able to use stem cells to treat injuries in the spinal cord or other parts of the body.

They may do this in several ways, including the following.

In some tissues, stem cells play an essential role in regeneration, as they can divide easily to replace dead cells. Scientists believe that knowing how stem cells work can help treat damaged tissue.

For instance, if someones heart contains damaged tissue, doctors might be able to stimulate healthy tissue to grow by transplanting laboratory-grown stem cells into the persons heart. This could cause the heart tissue to renew itself.

One study suggested that people with heart failure showed some improvement 2 years after a single-dose administration of stem cell therapy. However, the effect of stem cell therapy on the heart is still not fully clear, and research is still ongoing.

Another investigation suggested that stem cell therapies could be the basis of personalized diabetes treatment. In mice and laboratory-grown cultures, researchers successfully produced insulin-secreting cells from stem cells derived from the skin of people with type 1 diabetes.

Study author Jeffrey R. Millman an assistant professor of medicine and biomedical engineering at the Washington University School of Medicine in St. Louis, MO said, What were envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin.

Millman hopes that these stem cell-derived beta cells could be ready for research in humans within 35 years.

Stem cells could also have vast potential in developing other new therapies.

Another way that scientists could use stem cells is in developing and testing new drugs.

The type of stem cell that scientists commonly use for this purpose is the iPS cell. These are cells that have already undergone differentiation but which scientists have genetically reprogrammed using genetic manipulation, sometimes using viruses.

In theory, this allows iPS cells to divide and become any cell. In this way, they could act like undifferentiated stem cells.

For example, scientists want to grow differentiated cells from iPS cells to resemble cancer cells and use them to test anticancer drugs. This could be possible because conditions such as cancer, as well as some congenital disabilities, happen because cells divide abnormally.

However, more research is taking place to determine whether or not scientists really can turn iPS cells into any kind of differentiated cell and how they can use this process to help treat these conditions.

In recent years, clinics have opened that offer different types of stem cell treatments. One 2016 study counted 570 of these clinics in the United States alone. They appear to offer stem cell-based therapies for conditions ranging from sports injuries to cancer.

However, most stem cell therapies are still theoretical rather than evidence-based. For example, researchers are studying how to use stem cells from amniotic fluid which experts can save after an amniocentesis test to treat various conditions.

The Food and Drug Administration (FDA) does allow clinics to inject people with their own stem cells as long as the cells are intended to perform only their normal function.

Aside from that, however, the FDA has only approved the use of blood-forming stem cells known as hematopoietic progenitor cells. Doctors derive these from umbilical cord blood and use them to treat conditions that affect the production of blood. Currently, for example, a doctor can preserve blood from an umbilical cord after a babys birth to save for this purpose in the future.

The FDA lists specific approved stem cell products, such as cord blood, and the medical facilities that use them on its website. It also warns people to be wary of undergoing any unproven treatments because very few stem cell treatments have actually reached the earliest phase of a clinical trial.

Historically, the use of stem cells in medical research has been controversial. This is because when the therapeutic use of stem cells first came to the publics attention in the late 1990s, scientists were only deriving human stem cells from embryos.

Many people disagree with using human embryonic cells for medical research because extracting them means destroying the embryo. This creates complex issues, as people have different beliefs about what constitutes the start of human life.

For some people, life starts when a baby is born, while for others, it starts when an embryo develops into a fetus. Meanwhile, other people believe that human life begins at conception, so an embryo has the same moral status and rights as a human child.

Former U.S. president George W. Bush had strong antiabortion views. He believed that an embryo should be considered a life and not be used for scientific experiments. Bush banned government funding for human stem cell research in 2001, but former U.S. president Barack Obama then revoked this order. Former U.S. president Donald Trump and current U.S. president Joe Biden have also gone back and forth with legislation on this.

However, by 2006, researchers had already started using iPS cells. Scientists do not derive these stem cells from embryonic stem cells. As a result, this technique does not have the same ethical concerns. With this and other recent advances in stem cell technology, attitudes toward stem cell research are slowly beginning to change.

However, other concerns related to using iPS cells still exist. This includes ensuring that donors of biological material give proper consent to have iPS cells extracted and carefully designing any clinical studies.

Researchers also have some concerns that manipulating these cells as part of stem cell therapy could lead to the growth of cancerous tumors.

Although scientists need to do much more research before stem cell therapies can become part of regular medical practice, the science around stem cells is developing all the time.

Scientists still conduct embryonic stem cell research, but research into iPS cells could help reduce some of the ethical concerns around regenerative medicine. This could lead to much more personalized treatment for many conditions and the ability to regenerate parts of the human body.

Learn more about stem cells, where they come from, and their possible uses here.

Read the original:
Stem cells: Therapy, controversy, and research

IPS Cell Therapy Comments Off on Stem cells: Therapy, controversy, and research | October 5th, 2021

One of the most common questions Ive gotten over the last decade is, how much does stem cell therapy cost? They actually seem most often to want to know more specifically how much itshould cost.

To try to authoritatively answer this now in 2021 we need data from the present and past along with expert perspectives.

These kinds of questions on what are common and reasonable prices have continued in 2021. However, the types of queries have also evolved as things have gotten more complicated. There are many layers to the question of cost, which I cover here in todays article. In the big picture, the most worrisome potential cost is to your health if you proceed with unproven stem cell injections.

Stem cell cost questions | Stem cells cost $2,500 to $20,000| Why do stem cells cost so much? | How have stem cell prices changed? | Stem cell supplement cost | FTC actions and patients as consumers | Does insurance or Medicare cover stem cell therapy? | Patient fundraising | Looking ahead will stem cell costs go down?| References

This post is the most comprehensive look at stem cell treatment cost and costs of related therapies that Ive seen on the web, especially factoring in our inclusion of historical polling data from past years here on The Niche. The above bullet point list is what is covered in todays post and you can jump to sections that interest you most by clicking on those table of contents bullet points.

You can also watch the video I made summarizing the key points of this post below.

Furthermore, it encompasses other important issues related to insurance, fundraising, and approaches to being a smart consumer. Keep in mind that almost all stem cell therapies outside the bone marrow/hematopoietic sphere are not FDA-approved. They mostly lack rigorous data to back them up too. So this post is definitely not recommending you get them. I advise against it, but many people still want info on cost.

Lets get started.

After more than a decade of blogging about stem cells from just about every angle, its interesting to consider trends in the types of questions I get asked. Beyond cost, I also often get asked How much of a stem cell treatment price does insurance cover?

Of course, insurance (or lack thereof) directly bears on cost too. Ill get more into insurance later in the post.

In a way its not so surprising that cost is so much on peoples minds now for a few reasons.

First, as compared to many years back, people now view stem cell injections as a more everyday thing. Stem cell therapy is often available just down the street at a local strip mall.

Back in 2010 and in the 5 or so years after that, people instead more often viewed stem cells as some amazing thing out of reach to them at that time. Now people view stem cell offerings through the lens of consumers.

Sadly, another major part of the reason for the change in perceptions of stem cell treatments is the tidal wave of stem cell clinics from coast to coast in the US selling unproven and sometimes dangerous offerings.

At the same time, some universities and large medical centers also sell stem cell or similar offerings that arent proven. Im worried that that number may be increasing too and patients who may be paying there for unproven stem cells way at the very high end of the cost spectrum, sometimes above $100K.

Other stem cell suppliers and clinics market stem cell-related stuff that isnt real stem cells such as platelet rich plasma or PRP (see my comprehensive guide to PRP including a helpful infographic here) or injections of often dead perinatal stem cell products.

For all these reasons about once every year or two, I do polling asking the readers of The Niche here about their experiences.

Ive done the polling again now in 2020 in a more comprehensive form.

To have a sense of cost, we need to ask patients certain questions. How much did you pay per injection? How many injections did you get? Where did you get them?

Keep in mind that the total cost of stem cell therapy is the product of the cost per injection times the # of injections. For instance, if a stem cell injection costs $8,000 and you get 10 injections, your total cost is $80,000.

Unfortunately, the unproven stem cell clinics generally do not volunteer data on how much they charge. They also often encourage patients to get many injections.

Our 2020 polling data (you can still participate and I will update this) for stem cell treatments are in the graphic above. Here are some highlights.

The self-reported responses on cost for stem cell treatments, as indicated by respondents to our 2020 polling, suggest the price has gone up.

While the most common answer in 2019 was $2,501-$5,000, in 2020 the most common response was $10,001-$20,000, while $2,501-$5,000 was close behind.

The percentage of people paying the most, more than $100,000, was only slightly (probably non-significantly) higher in 2020, but both in 2019 and 2020 the percentage of people paying over $100K was much higher than in 2018 polling.

Keep in mind this is the cost per injection so how many injections do patients typically get? While the number of injections reported most commonly was 1 in both 2019 and 2020, in 2020, the second most common answer was 6-10 injections, a big boost from 2019. Again, more injections end up multiplying things up to boost the total cost. Only a few people in the polling had many injections, but in my view it is still striking to see anyone say theyve received more than 20 stem cell injections.

For comparison, the 2019 polling can be found here, but some of the key results are captured in a combo screenshot Ive included here. I got a lot more responses to the polling in 2019 so that makes me more confident in the data than in the 2020 polling so far, but I hope well get more responses moving forward in 2020 and if we do, again Ill update the info in this post.

What you can see from 2019 is that a plurality of respondents reported getting one stem cell injection, but 60% of people nonetheless got more than one stem cell injection.

Remarkably about 1 in 20-25 people received more than 20 stem cell injections.

About another 1 in 20 people got 6-20 injections. I find this amount of repeat injections to be surprising and concerning as it amplifies health and financial risks.

In terms of cost per injection, the results are pretty similar to 2018 (see at right below) on the whole.

This kind of polling isnt super scientific, but can gauge trends. Unfortunately, I havent really seen much other published data on stem cell clinic costs in actual journals.

I dont know if its noise or not, but the percentage of people paying over $100K is about 2-fold higher in 2019 versus 2018.

There are more people may be paying $10K-$20K as well now in 2020 vs. 2019 or 2018.

There is growing interest from the public in stem cell supplements. I did a post on this earlier in 2020 so take a look here, which was essentially a review of stem cell supplements like Regenokine. In terms of cost, while supplements are far less expensive than getting stem cell, PRP, or exosome injections, supplements are still pricey for what you get. Its not unusual to pay $100 for a small bottle of stem cell supplements, the other factor to consider is that these supplements generally have no solid, published data behind them so you might as well be paying $100 for water. Its unclear what risks taking these supplements might bring as well.

On the economic side, you might think that the feds like the FTC would be actively pursuing false or even fraudulent marketing of stem cells via the web and other kinds of advertising, but in total so far the FTC to my knowledge has only taken relatively few actions such as this one. and then some letters for COVID-related marketing of stem cells and other biologics earlier this year in 2020.

Oddly, there were just that a couple blips of FTC activity, especially considering the sea of questionable stem cell clinic-related ads out there. This ranges from major newspapers to inflight magazines to mobile ads on a stem-cell-mobile to television. Then of course there are the infomercial seminars.

Patients should also view themselves as consumers. Savvy customers considering paying money to stem cell clinics should do their homework. I often tell patients to use at a minimum the kinds of tough standards they bring to the car-buying process. Over the last few years Consumer Reports has been interested in the stem cell treatment world and done some reporting that is worth reading.

A common question I hear is the following: is stem cell therapy covered by insurance? Unfortunately for patients desperate to try stem cells, insurance generally does not provide any coverage, which often leads them to take extreme financial measures. These steps can include fundraising (more below).

In my view, the Regenexx brand has made a big deal out of how some employers contribute towards costs of their clinics offerings. Im not so clear on where that stands today in 2020.

Does Medicare cover stem cell therapies? Medicare will generally cover the cost of established bone marrow transplantation type therapies. However it does not cover unproven stem cell therapies.

Patients are often reaching out to me so I know that many of them have gone to extraordinary measures to raise the money to pay to unproven stem cell clinics. Its painful to think about what little they get in return. Since we are by definition talking about unproven medical procedures here, in my view this money is largely down the drain.

If you have other data on stem cell economic issues such as what patients pay please let me know. Then theres the issue of what it actually costs the clinics per injection and in turn: whats their profit margin?

What ends up happening is that patients take out second mortgages on their houses, try to collect funds from friends and relatives, or turn to online fundraising. The internet fundraising efforts most often end up on GoFundMe. This is a trend Ive been noticing for years. Some colleagues even published a paper on this trend, a very interesting and an important read. The paper is Crowdfunding for Unproven Stem CellBased Interventions in JAMA by Jeremy Snyder,Leigh Turner , and Valorie A. Crooks. Heres a key passage:

As of December 3, 2017, our search identified 408 campaigns (GoFundMe=358; YouCaring=50) seeking donations for stem cell interventions advertised by 50 individual businesses. These campaigns requested $7439308 and received pledges for $1450011 from 13050 donors. The campaigns were shared 111044 times on social media. Two campaigns were duplicated across platforms but shared separately on social media. Of the 408 campaigns, 178 (43.6%) made statements that were definitive or certain about the interventions efficacy, 124 (30.4%) made statements optimistic or hopeful about efficacy, 63 (15.4%) made statements of both kinds, and 43 (10.5%) did not make efficacy claims. All mentions of risks (n=36) claimed the intervention had low/no risks compared with alternative treatments.

Supposedly GoFundMe has taken some steps to lower the often ethically thorny stem cell fundraising on its site, but Im not sure how much it has changed.

There is pressure on stem cell clinics now in 2021 in large part due to two factors. These could drive costs down or up depending on how things play out. First, the FDA is much more active against unproven stem cell clinics. This may mean more money from the clinics going toward paying attorneys or FDA compliance experts. Youd think this might drive costs up. However, the still large number of clinics may keep pressure to stay with keeping price tags lower.

The second factor is the COVID-19 pandemic, which has forced many clinics to stop injections temporarily. While a surprising number of clinicsI did by phone were still open in a small informal survey, others were in a holding pattern. This may lower supply which could raise prices. But I think demand is likely way down as many patients stay home to avoid COVID risks. This could be temporary though. As things start re-opening, as they are now, the clinics may be able to capitalize on pent-up demand.

To sum up, the answer to the question, How do stem cells cost? is largely driven by clinic firms aiming to profit. Overall, clinics will charge what they think patients will pay them, which will always be a moving target. I urge patients to be cautious both medically, talking to their doctors, and financially.

Link:
How much does stem cell therapy cost in 2021? - The Niche

IPS Cell Therapy Comments Off on How much does stem cell therapy cost in 2021? – The Niche | October 5th, 2021

In conversation with Dr Koji Tanabe, Founder and CEO, I Peace, Inc., The United States/Japan

To make the trial investments more meaningful and to avoid ambivalence in animal models, medical science is adopting novel in vitro models of specialised human pluripotent cell lines. Pluripotent stem cells(PSCs) have the agility to expand indefinitely and differentiate into almost any organ-specific cell type. iPSC-derived organs andorganoidsare currently being evaluated in multiple medical research arena like drug development, toxicity testing, drug screening, drug repurposing, regenerative therapies, transgenic studies, disease modeling and more across clinical developments. Innovative pharmacovigilance methodologies are preferring induced pluripotent stem cells (iPSCs) for pre-clinical and clinical investigational studies. Global Induced Pluripotent Stem Cell (iPSC) market is expected to reach $2.3 B by 2026. The iPSC market inAsia-Pacificis estimated to witness fast growth due to increasing R&D projects across countries likeAustralia,JapanandSingapore.

I Peace, Inc. a Palo Alto-based global biotech company with its manufacturing base in Japan, has succeeded in developing and mass-producing clinical grade iPS cells through its proprietary iPS cell manufacturing services. The human iPSC (hiPSC) lines at I Peace leverage differentiated cells across clinical research and medical applications. Biopsectrum Asia discovered more about Japan's stem cell manufacturing ecosystem with Dr Koji Tanabe, Founder and CEO, I Peace, Inc., (The United States/Japan). Tanabe earned his doctorate under Dr Shinya Yamanaka, a Kyoto University researcher who received the 2012 Nobel Prize in Physiology or Medicine for discovery of reprogramming adult somatic cells to pluripotent cells. I Peace is focusing on this Nobel Prize-winning iPSCs technology where Tanabe had played a key role in generating the worlds first successful human iPSCs as one of the team members and is currently industrialising it in the US and Japan.

How do you define Japans Stem cell manufacturing dynamics aligning with regional and APAC market potential?

We believe that human cells play a pivotal role in next-generation drug therapy. Clinical trials of iPSC applications are in full swing not only in Japan, but worldwide as well. In the US, the momentum of clinical trial research is astounding. Yet, mass production of GMP compliant cell products remains a challenge. Entry into this venture is no easy task. As a contract development and manufacturing organisation (CDMO), I Peace is geared to tackle that challenge and become the pioneer of mass production technology of clinical grade cell products.

Can you elaborate I Peaces cost-effective proprietary stem cell synthesis solution and its manufacturing scale?

The key advantage of iPSCs is the ability to create pluripotent cells from an individuals own cells. Furthermore, iPSCs can multiply indefinitely and evolve into any type of cell, making iPSCs an ideal tool for transplant and regenerative medicine and drug research. However, clinical applications of iPSCs to date, utilise heterogenic transplantation. It is because manufacturing of just one line of iPSCs requires a cost intensive clean room to be occupied for several months. Manufacturing process complexities also pose a barrier to cost reduction and mass production.

In contrast, I Peace has developed a proprietary, fully automated closed system for iPS manufacturing, enabling cost-effective production of multiple lines of iPSCs from multiple donors in a single room. Within a few years, we expect to manufacture several thousand lines of iPSCs simultaneously in a single room. With this technology, I Peace can efficiently generate an ample supply of various iPSCs for heterogenic transplant, while also fostering a society where everyone can bank their own iPSCs for potential medical use.

How does I-Peace better position its businesses objectives and go-to-market strategies?

I Peaces manufacturing facility and its processes have undergone rigorous audits and are certified to be in compliance with GMP guidelines of the US, Japan, and Europe. We have the capacity to manufacture clinical-grade iPSCs and iPSC-derived cells for clinical use in the global market. Our manufacturing staff have unparalleled expertise in the manufacturing of iPSCs, and their knowledge and experience make it possible to mass produce high quality clinical-grade iPSCs in the shortest possible time. Additionally, we streamlined the iPSC use licensing scheme to expedite collaborative ventures with downstream partners. We believe these strategies position I Peace as a global leader in iPSC technology.

How do you outline the concept of democratising access to iPSC manufacturing?

At I Peace, we envision a world in which everyone would possess their own iPSCs and if needed, receive autologous transplant medication using their own iPSC. We believe in the importance of raising awareness of Nobel Prize winning iPSC technology and we think much more needs to be done. We need to enlighten the public about iPSCs - what they are, how they are created, and how they play a role in next-generation medical therapies. We also need to underscore the benefits of early banking ones own iPSCs, such as autologous transplant and the fact that cells taken in the early stages of life are preferable over cells collected later in life.

To democratise iPSC access, it is also important to expedite application research. We work closely with downstream partners, and support their iPSC-derived drug therapy development efforts by providing iPSCs to meet their needs. We also collaborate with downstream partners in the development of promising therapies including the use of T-cells for cancer therapy, cardiomyocytes for the treatment of heart disease, and neurocytes for neurological disease.

What is your outlook around boosting public-private stakeholders initiatives to encourage awareness on stem-cell-based therapeutics?

iPSC research has advanced tremendously over the past 16 years, and even more so since Dr Shinya Yamanakas Nobel Prize award in 2012. The acceleration of applied research is paving the way for stem cell-based therapeutics to become a common treatment modality in the near future. As human cell manufacturing requires specialised professional skills and knowledge, it is important to promote functional specialisation. These specialisations include donor recruiting, cell manufacturing (where I Peace is the key player), and implementing cell transplant as a medical practice. We believe that creating a systematic industry structure will build awareness and further drive the growth of stem cell-based therapy.

Can you brief Japans licensing key notes to manufacture and process clinical-grade cells in the region?

Japan enacted three laws to promote the use of regenerative medicine as a national policy:

1) The Regenerative Medicine Promotion Act -- representing the country's determination to promote regenerative medicine;

2) The Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act); and

3) The Act on the Safety of Regenerative Medicine (RM Act). The U.S. also has various tracks such as the Regenerative Medicine Advanced Therapy (RMAT) Designation, Breakthrough Therapy designation, and Fast Track designation.

Of significance, the PMD Act enables a fast-track for regulatory approval of regenerative medicalproducts in Japan. In compliance with the RM Act, I Peace was audited by the PMDA and licensed by the Ministry of Health, Labour, and Welfare to manufacture specific cell products.

Because cell product manufacturing regulations are not standardised globally, cell therapy developers are forced to source GMP iPSCs for each market. I Peace however, has overcome this hurdle. We have built in compliance with global GMP regulations, including FDA's cGMP regulations per 21 CFR 210/211 in our operation. As a result, we can provide cells for global use in multiple markets, accelerating both product development and regulatory approval.

Hithaishi C Bhaskar

hithaishi.cb@mmactiv.com

See original here:
"Stem cell-based therapeutics poised to become mainstream option - BSA bureau

IPS Cell Therapy Comments Off on "Stem cell-based therapeutics poised to become mainstream option – BSA bureau | October 5th, 2021

Every person, every mouse, every dog, has one unmistakable sign of aging: hair loss. But why does that happen?

Rui Yi, a professor of pathology at Northwestern University, set out to answer the question.

A generally accepted hypothesis about stem cells says they replenish tissues and organs, including hair, but they will eventually be exhausted and then die in place. This process is seen as an integral part of aging.

Instead Dr. Yi and his colleagues made a surprising discovery that, at least in the hair of aging animals, stem cells escape from the structures that house them.

Its a new way of thinking about aging, said Dr. Cheng-Ming Chuong, a skin cell researcher and professor of pathology at the University of Southern California, who was not involved in Dr. Yis study, which was published on Monday in the journal Nature Aging.

The study also identifies two genes involved in the aging of hair, opening up new possibilities for stopping the process by preventing stem cells from escaping.

Charles K.F. Chan, a stem cell researcher at Stanford University, called the paper very important, noting that in science, everything about aging seems so complicated we dont know where to start. By showing a pathway and a mechanism for explaining aging hair, Dr. Yi and colleagues may have provided a toehold.

Stem cells play a crucial role in the growth of hair in mice and in humans. Hair follicles, the tunnel-shaped miniature organs from which hairs grow, go through cyclical periods of growth in which a population of stem cells living in a specialized region called the bulge divide and become rapidly growing hair cells.

Sarah Millar, director of the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, who was not involved in Dr. Yis paper, explained that those cells give rise to the hair shaft and its sheath. Then, after a period of time, which is short for human body hair and much longer for hair on a persons head, the follicle becomes inactive and its lower part degenerates. The hair shaft stops growing and is shed, only to be replaced by a new strand of hair as the cycle repeats.

But while the rest of the follicle dies, a collection of stem cells remains in the bulge, ready to start turning into hair cells to grow a new strand of hair.

Dr. Yi, like most scientists, had assumed that with age the stem cells died in a process known as stem cell exhaustion. He expected that the death of a hair follicles stem cells meant that the hair would turn white and, when enough stem cells were lost, the strand of hair would die. But this hypothesis had not been fully tested.

Together with a graduate student, Chi Zhang, Dr. Yi decided that to understand the aging process in hair, he needed to watch individual strands of hair as they grew and aged.

Ordinarily, researchers who study aging take chunks of tissue from animals of different ages and examine the changes. There are two drawbacks to this approach, Dr. Yi said. First, the tissue is already dead. And it is not clear what led to the changes that are observed or what will come after them.

He decided his team would use a different method. They watched the growth of individual hair follicles in the ears of mice using a long wavelength laser that can penetrate deep into tissue. They labeled hair follicles with a green fluorescent protein, anesthetized the animals so they did not move, put their ear under the microscope and went back again and again to watch what was happening to the same hair follicle.

What they saw was a surprise: When the animals started to grow old and gray and lose their hair, their stem cells started to escape their little homes in the bulge. The cells changed their shapes from round to amoeba-like and squeezed out of tiny holes in the follicle. Then they recovered their normal shapes and darted away.

Sometimes, the escaping stem cells leapt long distances, in cellular terms, from the niche where they lived.

If I did not see it for myself I would not have believed it, Dr. Yi said. Its almost crazy in my mind.

The stem cells then vanished, perhaps consumed by the immune system.

Dr. Chan compared an animal's body to a car. If you run it long enough and dont replace parts, things wear out, he said. In the body, stem cells are like a mechanic, providing replacement parts, and in some organs like hair, blood and bone, the replacement is continual.

But with hair, it now looks as if the mechanic the stem cells simply walks off the job one day.

But why? Dr. Yi and his colleagues next step was to ask if genes are controlling the process. They discovered two FOXC1 and NFATC1 that were less active in older hair follicle cells. Their role was to imprison stem cells in the bulge. So the researchers bred mice that lacked those genes to see if they were the master controllers.

By the time the mice were 4 to 5 months old, they started losing hair. By age 16 months, when the animals were middle-aged, they looked ancient: They had lost a lot of hair and the sparse strands remaining were gray.

Now the researchers want to save the hair stem cells in aging mice.

This story of the discovery of a completely unexpected natural process makes Dr. Chuong wonder what remains to be learned about living creatures.

Nature has endless surprises waiting for us, he said. You can see fantastic things.

Excerpt from:
Losing Your Hair? You Might Blame the Great Stem Cell Escape. - The New York Times

Skin Stem Cells Comments Off on Losing Your Hair? You Might Blame the Great Stem Cell Escape. – The New York Times | October 5th, 2021

As a beauty writer and longtime skincare fanatic, Ive subscribed to various multi-step routines. Fast forward to having a baby and the general day-to-day life upheaval that comes along with it, and my definition of a worthwhile personal beauty regimen has changed a bit. While I still enjoy trying new products and learning about innovations in the beauty space, I find myself with less time (and patience) for the more laborious treatments and layering routines, and more interest in noticeable efficacy and multitasking capabilities.

The most effective skincare products and tools are great for paring down your routineand also ... [+] saving you some precious minutes in your day.

And whether youre a busy mom or simply short on me time these days (who isnt?), there are a myriad of tried-and-true products that get the job done without requiring a ton of effort on your part. From Herauxs next-level anti-inflammaging serum to NuFaces skin-smoothing device, these standout skincare products and tools are ideal for a results-driven regimen thats effective enough to knock a few steps off your routineand save you some precious minutes in your day.

Since its launch seven years ago, this antioxidant-rich hydrating facial oil has remained a cult favorite for anyone who wants an instant glow, with the added benefit of skin soothing, balancing and repair. Infused with 22 active botanical and essential oils, the lightweight yet potent treatment can help with everything from acne to sun damage. And when applied using founder April Gargiulos signature push-press technique, it feels like a simple yet luxurious way to start and end the day.

Like the brands Trinity device, the NuFace Fix uses microcurrent technology at a gentler level to help reduce the look of fine lines and wrinkles on the more delicate areas of the face: on the forehead, between brows and around the eyes and lips (filler-free plumping, anyone?). Its sleek, compact shape combined with ease of use makes it a no-brainer for skin smoothing results in a matter of minutes. Plus, it holds an ample 120-minute charge, which amounts to a couple months worth of use before needing to plug it ini.e. no fumbling with cords or a hefty device on a regular basis.

The latest product in Kate McLeods sustainably packaged, handcrafted self care collection and the first to focus on skincare, the Face Stone is essentially a waterless moisturizer that melts on contact with skin. A rich blend of nourishing and antioxidant ingredients like blue tansy, kokum butter and plum kernal borage helps even and soothe stressed skinsomething we could all use these days. An added bonus? Its solid form and shape makes it a natural massaging tool, making it ideal for a morning pick-me-up or the start of an evening wind-down ritual.

While it covers your mineral-based broad spectrum sunscreen needs, this multitasker does much more than that. The unique product uses the U Beautys proprietary Sun-Siren Capsule Technology to help reduce hyperpigmentation, discoloration and dark spots (whether from pregnancy melasma or suntanning sins of the past) while also shielding against UVA, UVB, infrared and blue light exposure. A little goes a long way with this rich balm-cream formula, and its hydrating enough to double as a moisturizer or primer by day and also great as an overnight spot treatment.

An excellent (and cleaner) dupe for Biologique Recherches oft-elusive Lotion P50, this Moon Juice exfoliator is a skin savior in its own right. The liquid formula includes glycolic, lactic and salicylic acids for gentle, pore-minimizing exfoliation paired with niacinamide and adaptogenic reishi to help boost the skins natural barrier. And besides looking pretty, the packaging is completely recyclable, from the sculptural cap and glass bottle to the outer carton.

January Labs is a clean beauty favorite for its science-backed, results-driven products that have long been favored by top aestheticians. Even those with more sensitive (or dry) skin can use this retinol serum without dealing with typical downsides (like redness, drying or peeling) thanks to its use of Retistar, a .5% retinol thats super effective yet non-irritating.

This at-home peel is as easy as can be, requiring a single once-over with the pre-soaked pad to revive dull skin. The duo of glycolic and salicylic acids provide skin-smoothing exfoliation while ingredients like chamomile and bilberry extract calm, soothe and help even skin tone. Pro tip: Use up excess product on any dry, flakey patches on arms and legs.

Created by stem cell biologists at the University of Southern California, this innovative serum features an anti-inflammaging HX-1 molecule thats combined with tried-and-tested ingredients like vitamin C, hyaluronic acid, peptides and red maple bark. The result? A silky, lightweight formula thats both rejuvenating (designed to help reduce the effects of stress and aging factors on skin) and preventative (strengthening stem cells on a molecular level).

The rest is here:
The Best Skincare Treatments For Time-Crunched Moms (Or Anyone Else Who Only Has Five Minutes To Spare) - Forbes

Skin Stem Cells Comments Off on The Best Skincare Treatments For Time-Crunched Moms (Or Anyone Else Who Only Has Five Minutes To Spare) – Forbes | October 5th, 2021

A recent article in the journal Nature credits Stanford physician-neuroscientist Sergiu Pasca, MD, with blazing a trail toward a more profound understanding of early brain development, and of what can go wrong in the process, using a cell-based research innovation he named "assembloids."

In 2015, Pasca and his colleagues published a paper in Nature Methods describing a fascinating feat: His tinkering with induced pluripotent stem cells, or iPS cells -- former skin cells transformed so that they've acquired an almost magical capacity to generate all the tissues in the body -- had borne a three-dimensional product. From these "magic" iPS cells grew a complex conglomerate of cells capable of modeling specific organs.

Pasca's particular interest was in the brain, and in the experiments detailed in the study, his lab had caused human iPS cells to multiply and differentiate into small spherical clusters of brain tissue suspended in laboratory glassware.

These clusters recapitulated the architecture and physiology of the human cerebral cortex -- the outermost layer of brain tissue, critical to perception, cognition and action. Pasca named these clusters, which grew to several millimeters in diameter and contained millions of cells, "cortical spheroids." Today, researchers around the world are using similar methodology to create models, broadly known as "organoids," to study other parts of the human body.

Two years later, in a study published in Nature, Pasca upped the ante by, first, generating a second kind of neural spheroid -- this time, representative of a deeper part of the developing forebrain called the subpallium -- and, second, by growing this kind of spheroid in conjunction with cortical spheroids, in the same dish.

To the researchers' amazement, spheroids of both types fused together, with nerve cells from subpallial spheroids migrating and poking extensions into the cortical spheroids and establishing working connections with nerve cells of a different type in the latter spheroids, just as occurs in fetal development.

"It's amazing that these cells already self-organize and know what they need to do," Pasca marveled in "Brain Balls," an article I wrote for our magazine, Stanford Medicine, a few years ago.

Pasca sensibly dubbed the two-fused-spheroid combos "assembloids," the Nature recap notes.

But why stop at two? Pasca has since created three-element assembloids composed of spheroids representative of cerebral cortex, spinal cord and skeletal muscle in order to model the circuitry of voluntary movement. He's also shown that stimulating the "cerebral cortex" spheroid can result in contraction of the "muscle" spheroid. (This accomplishment was published in Cell in late 2020.) He has explored other assembloid combinations, as well, such as the fusing of cortical spheroids with spheroids representing the striatum, a brain structure implicated in regulating our movements and responses to rewarding and aversive stimuli.

Because each spheroid begins with skin cells, they can be grown on a personalized basis -- and can therefore be extracted from patients with neurological disorders known or suspected to spring from early developmental aberrations (such as autism or schizophrenia). The cells can then be used to create models to probe these disorders' molecular, cellular and circuit-based deviations from the pathways of normal brain development, allowing scientists to study the brain in way they could never do with a living patient.

From the Nature article:

Assembloids are now at the leading edge of stem-cell research. Scientists are using them to investigate early events in organ development as tools for studying not only psychiatric disorders, but other types of disease as well.

An assembloid is by no means a complete, working brain. But, the article notes, "Pasca stands by the aphorism that all models are wrong, and some are useful. 'There's been important progress in the field in a short period of time,' he says."

Photo courtesy of the Pasca laboratory

Originally posted here:
Stanford neuroscientist's 'assembloids' pave the way for innovative brain research - Scope

Skin Stem Cells Comments Off on Stanford neuroscientist’s ‘assembloids’ pave the way for innovative brain research – Scope | October 5th, 2021

Fall is here, and now is the perfect time to upgrade your beauty routine for the cooler temperatures. Here are a few of our favorite products:

Parfums de Marly

The famed perfume house founded by Julien Sprecher will launch sensual Oriana on September 12th. Packaged in a hot pink bottle, the airy and dreamy fragrance is captivating withnotes of orange blossom, marshmallow, and Chantilly cream. Available on parfums-de-marly.com and Saks Fifth Avenue. $320.

ILONA

This innovative skincare brand continuously seeks out innovative ingredients and technologies from around the world and incorporates them into premium high-performance formulas like the BEYOND C Corrective Serum. This reincarnating serum is housed in a beautiful dual vessel package. One side is black, the other gold with each containing corrective technologies that reach maximum potency at the moment of unity.

The black side contains a novel probiotic and micronized niacin that fortifies skin defenses, intensifies cellular activity, quells inflammation, and amends blotchiness. The gold vessel contains a patented, hyper-potent, permeable form of vitamin C that helps brighten, fade age spots, even skin tone, and protect against oxidation. $132.

Heraux

This innovative product was created by Heraux Co-Founder Dr. Ben Van Handel, a Stem Cell Biologist at the University of Southern California and leading inflammaging researcher. Dr. Handel notes that Retinols are anti-inflammatory at the molecular level, acting as antioxidants and blocking hyperactivation of the immune system. HX-1, the proprietary ingredient in HerauxsMolecular Anti-Inflammaging Serum, acts to shield skin stem cells from pro-inflammaging stressors and concurrently supports the youthful function of stem cells. The regenerative program enabled by HX-1 promotes the secretion of collagen and elastin as well as improved skin barrier function.

Kimberly Fisher is a Pursuitist contributor. As a freelance writer and on-camera host, Kimberly has traveled the world and has published over 400 articles in over 44 publications including Sherman's Travel, Huffington Post, Just Luxe, Luxury Lifestyles UK, eHow, Examiner, Food Wine Travel Magazine, Luxe Beat, NiteGuide, Ocean View, and USA Today. Disclosure: Kimberly is employed by Remy Cointreau Americas.

Link:
3 of the Best Fall Beauty Buys - Pursuitist

Skin Stem Cells Comments Off on 3 of the Best Fall Beauty Buys – Pursuitist | October 5th, 2021

Facial serums are skin care products that the skin can absorb rapidly. They are formulated to contain high doses of ingredients, including actives such as vitamin C and retinol. They are not moisturizers. Instead, they are an additional step in a skin care routine selected to address specific skin concerns.

While many facial serums make claims about their benefits, limited scientific data is available to support these claims. The potential uses and benefits of a serum will depend on the ingredients and their concentration.

Many serums use active ingredients such as:

Common issues face serums claim to address include acne, rosacea, and signs of aging such as wrinkles.

One study of a facial serum targeting fine lines and wrinkles found that after 12 weeks, women showed statistically significant improvements in:

Face serums are generally considered safe. They are available without a prescription. However, because face serums deliver concentrated doses of active ingredients such as vitamin C or hyaluronic acid, people should exercise caution when trying them for the first time.

Pregnant people should exercise caution when selecting skin care products. Using products made with concentrated forms of vitamin A, such as retinol, can harm a developing fetus. Pregnant people should avoid skin care products that contain retinoids or other harmful ingredients.

People who are already using prescription or high dosage skin care products should check with their healthcare providers before using face serums to ensure they are not taking in unhealthy levels of powerful ingredients, such as retinoids.

When introducing a new active ingredient to the skin, there is a possibility of side effects such as:

If a person experiences these symptoms, they should reduce the frequency and dosage of the serum or stop using it altogether if symptoms do not reduce.

The American Academy of Dermatology recommends trying just one new product, like a facial serum, at a time. Starting several new products all at once, particularly anti-aging products, can irritate the skin and make it difficult to determine which products are beneficial.

It is also helpful to perform a patch test for a week before using a new product on facial skin. A patch test involves applying small amounts of the new product on the inner forearm for a few days to check for reactions.

A skin serum will not be effective if it is not used properly. The best time to apply face serum is after cleaning the skin and before applying moisturizer.

Facial serums are concentrated, so people should only use a small amount to cover the facial skin.

Learn more about skin care routines here.

No single skin care product can address all skin health needs. To pick out the best face serum, a person should first decide what skin concern they want to address, such as wrinkles or acne.

Look for a face serum that is a good fit for individual concerns and needs. For example, a person should choose a face serum that suits their skin type, such as oily, dry, combination, or aging.

Some people may wish to find products that are hypoallergenic and noncomedogenic, which means they are less likely to cause allergic reactions or acne.

Products do not have to be expensive to be effective, and serums are available to suit various budgets.

Please note that the writer of this article has not tried these products. All information presented is purely research-based.

This is an oil-free vitamin C face serum designed for people with oily or blemish-prone skin.

SkinCeuticals claims this serum can reduce skin oiliness and wrinkles, and improve skin texture.

The ingredients include:

This serum costs $166 for a 30ml bottle.

Made with Avene Thermal Spring Water, this water-gel serum is safe for adolescents and adults.

It is suitable for oily skin and should be used after cleansing in the morning and evening.

Avena claims that this product can be used safely alongside other acne treatments and can reduce the appearance of pores.

This serum costs $28.00 for 30ml.

This antioxidant face serum is fragrance- and oil-free, and certified cruelty-free.

Drunk Elephant claims it can reduce the signs of sun damage and aging while hydrating the skin. It stays active on the skin for up to 72 hours and should be applied in the morning.

Customers must mix a powder and liquid to create the fresh activated serum.

This serum costs $78.00 for 28ml.

This face serum contains aloe, vitamin A, niacinamide, vitamin C, vitamin E, tea tree oil, and other vitamin and herbal ingredients.

Klur states that this serum may even out skin texture, helps calms inflammation, and increases skin clarity.

People should use it at night and no more than 3 times a week.

This serum costs $110.00 for 30ml.

This serum uses forms of retinoid that The Ordinary states may reduce the signs of aging better than other retinoid products, without causing irritation.

The company recommends people patch test the serum, before using it on facial skin. People should not use it in combination with other retinoid products.

Use only in the evening after cleansing, and refrigerate after opening.

This serum is vegan and free from oil, silicones, nuts, and gluten.

This low-cost serum sells for $9.80 for 60ml.

This cruelty-free skin serum contains milk protein, seaweed extract, and arnica. Ren claims it may calm and soothe the skin while reducing redness and irritation.

It should be used morning and/or night before moisturizing.

This serum costs $58.00 for 30ml.

True Botanicals claims that this anti-aging serum may reduce the appearance of fine lines and wrinkles.

It uses natural antioxidants such as chebula, elderberry, ginger, and echinacea to help strengthen the skins immunity to signs of aging.

After morning and evening cleansing, users can apply one half or full drop to their faces.

This serum costs $90.00 for 30ml.

Skin Authority claims that this lightweight serum reduces the appearance of fine lines, by plumping skin folds and smoothing skin texture.

This serum is designed for use after morning cleansing.

This serum costs $155.00 for 15ml.

Peach and Lily claims that this serum can brighten the skin and reduce the appearance of dark spots.

It contains various ingredients from botanical sources, including green tea extracts, mushrooms, and arbutin. It also contains niacinamide.

It is suitable for all skin types.

This serum costs $39.00 for 50ml.

SkinCeuticals claims that this serum may reduce the appearance of dark spots and improves skin tone.

Ingredients include:

It is suitable for people with all skin types.

This serum costs $98.00 for 30ml.

Bioderma claims that this face serum may increase the skins ability to retain moisture. Made specifically for people with dry skin, it is noncomedogenic, meaning it will not block pores.

People can use this serum in the morning and evening.

This serum costs $27.99 for 40ml.

This serum is suitable for use by people with all skin types. Eminence claims that this face serum helps reduce the appearance of sun-induced skin damage.

Its active ingredients include vitamin C and other antioxidants, which work together to brighten the skin and improve the appearance of fine lines and wrinkles.

This serum costs $110.00 for 30ml.

Original post:
12 of the best face serums 2021 - Medical News Today

Skin Stem Cells Comments Off on 12 of the best face serums 2021 – Medical News Today | October 5th, 2021

A man went to a clinic in Mannheim, Germany, where tests found that the rash on his hands and elbows was in fact leukaemia cutis, where the cancer cells are in the skin tissue

Image: NEJM)

A man suffering from a nasty skin rash on his hands and elbows that looked like psoriasis found that it was actually a form of leukaemia.

The 65-year-old went to a dermatologist in Mannheim, Germany, due to the red patches that had developed on the back of his hands and arms and he later found the worrying diagnosis that it was leukaemia cutis.

Tests done at the hospital showed that he had a high white-cell count along with a low number of platelets, it is reported.

The case was published in the New England Medical Journal where it said that a diagnosis of leukaemia cutis was made.

While extremely rare, the condition means that the leukaemia cells are in the skin tissue.

It is found to happen in around three percent of leukaemia cases where the rash has been found on skin including the arms, back or face.

Image:

Other leukaemia symptoms include fever, tiredness and susceptibility to infections.

But in the case of the 65-year-old in Germany, he only had the rash on his hands and elbow.

The New England Medical Journal stated: "A diagnosis of leukemia cutis was made, and the patient was urgently referred to the oncology clinic.

"The patient received a diagnosis of chronic myelomonocytic leukaemia and underwent stem-cell transplantation.

"Two weeks after the transplantation, the patients skin changes had resolved, and the cancer has been in remission since."

Leukaemia Care UK said that usually patients who have the cancer and find rashes do not have this particular condition.

It stated: Leukaemia cutis is very rare, occurring in only about three percent of total cases of leukaemia.

"With this in mind, it is unsurprising that most lesions seen in leukaemia patients are not leukaemia cutis.

In fact, most lesions (40%) seen in leukaemia patients are caused by other complications of leukaemia.

It continued: In the rare occasion that leukaemia cutis occurs, the patient will normally have already been diagnosed with leukaemia.

"However, in seven percent of cases of leukaemia cutis, the skin lesion is the very first symptom of a blood cancer. This is sometimes referred to as aleukaemic leukaemia cutis.

See original here:
Man discovers nasty red rash on his hands and elbows is potentially fatal - The Mirror

Skin Stem Cells Comments Off on Man discovers nasty red rash on his hands and elbows is potentially fatal – The Mirror | October 5th, 2021

Kyoto A drug discovered through a method using induced pluripotent stem cells, or iPS cells, from sufferers of amyotrophic lateral sclerosis (ALS) was effective in stopping the progression of the neurological disease in five out of nine patients in a clinical trial, a research team at Kyoto University said Thursday.

While drugs that slow down the progression of amyotrophic lateral sclerosis, also known as Lou Gehrigs disease, have been used in the past, this is the first time that a chronic myeloid leukemia drug called bosutinib has been found to stop its progression, according to the team.

Haruhisa Inoue, a professor of neurology at Kyoto University leading the team, said that larger clinical trials will be needed to determine if the drug can be put to practical use, but We are now looking at the possibility of being able to control ALS with the power of science.

The team reproduced the disease by culturing iPS cells derived from the skin of patients into motor neurons. They then tested a series of drug compounds on the cells to find that bosutinib was effective in slowing down the progression of ALS.

The drug was administered for around three months to nine patients who were in the early stages of the disease and showing signs of deterioration. Progression of the disease stopped in five patients during the treatment period, while four patients continued to deteriorate at the same pace as before.

A comparison of the blood samples from both sets of patients showed that they had differing amounts of a protein unique to nerve cells before the drug was administered. Researchers plan to conduct clinical trials with larger groups while adjusting the dosage and other conditions in the future.

There are about 9,000 people in Japan who suffer from ALS. The disease causes motor neurons to progressively die, resulting in paralysis, with many patients requiring a ventilator to stay alive. Its exact cause is unknown, and no fundamental treatments have been established.

In a time of both misinformation and too much information, quality journalism is more crucial than ever.By subscribing, you can help us get the story right.

PHOTO GALLERY (CLICK TO ENLARGE)

More here:
Drug that stops ALS progression found using iPS cells from patients - The Japan Times

Skin Stem Cells Comments Off on Drug that stops ALS progression found using iPS cells from patients – The Japan Times | October 5th, 2021

Photo: Francis Collins, by NIH Image Gallery, via Flickr.

Francis Collins, Director of the National Institutes of Health (NIH),has just announcedhis intention to step down at the end of 2021 after more than 12 years heading the agency. The accolades are already rolling in. Noted evangelical political commentator David French, for example, rushed to praise Collins as a national treasure.

But Collinss real legacy is anything but praiseworthy, and the tendency of figures in the faith community to ignore his real record is far from admirable.

This year of all years should have made the truth about Francis Collins clear. Last month, documents were released suggesting that top National Institutes of Health (NIH) officials may haveliedwhen they denied that the NIH had funded gain of function research in Wuhan, China, that could have resulted in a pathogen that could infect humans.

After reviewing the documents, Rutgers University biologist Richard Ebright had a blistering response: The documents make it clear that assertions by the NIH Director, Francis Collins, and the NIAID Director, Anthony Fauci, that the NIH did not support gain-of-function research or potential pandemic pathogen enhancement are untruthful.

It was another blow to the reputation of Collins in a year when his agency has faced multiple scandals and controversies.

Among evangelical Christians and other people of faith in America, Collins has long been the equivalent of a rock star. But Collinss days of glory as a non-partisan role model, especially for the faith community, may be numbered and its not just because of the latest scandal over the origins of COVID-19.

In recent months, Collinss agency has become embroiled in controversies over its funding of stomach-churning medical experiments involving body parts harvested from aborted babies. The disclosures about the experiments followed Collinssrepealearlier this year of restrictions on the use of aborted fetal tissue in NIH-funded research.

Collins has also stirred controversy with his increasingly shrill attacks on unvaccinated Americans and his support for harsh mandatory vaccination policies that will require the firing of employees who choose not to be vaccinated with a COVID-19 vaccine.

The former head of the Human Genome Project, Collins catapulted to fame (and the cover ofTimeMagazine) in 2000 with the announcement of a working draft of the sequence of the human genome.He then became a hero to many Christians with the publication in 2006 of his bookThe Language of God, which recounted his journey from atheism to Christianity.

In an increasingly polarized national environment, Collins is one of the rare heads of a major federal agency to serve under both Republican and Democratic Presidents. Appointed by President Obama to head the NIH in 2009, Collins continued in that role under President Trump and now President Biden. He has regularly drawn praise from lawmakers on both sides of the aisle. At gatherings of evangelical Christians, he has been known to strum the guitar and sing worship songs and receive the adoration of attendees. At one 2019 eventit was reportedthat conference participants lined up for selfies with him.

In 2020, Collins wasawarded the prestigious Templeton Prize, worth more than $1.3 million, for his work integrating science and faith. Previous recipients of the prize have included Mother Teresa, John Polkinghorne, Charles Colson, and Aleksandr Solzhenitsyn.

Among secular as well as religious journalists, Collins often receives what verges on fawning treatment. A writer forThe New Yorkergushedthat Collins is a model of geek cool. He likes big, noisy motorcycles, and, despite a mild manner, he is famously unself-conscious. At the unlikeliest moments, he will strap on a guitar and accompany himself in song, often a tune he has composed for the occasion.

This year, however, Collinss reputation has taken continued beatings, not just because of evasive answers about the role of the NIH in gain-of-function research in China, but also because of publicity around NIH-funded experiments that many Americans, especially people of faith, would find horrific.

In May, reports surfaced aboutmacabre NIH-funded experimentsthat utilized body parts collected fromaborted human fetuses to createhumanized mouse and rodent models with full-thickness human skin.For the experiments, researchersat the University of Pittsburghcut into tiny pieces human fetal spleen, thymus, and liver organs and then transplanted the tissues and hematopoietic stem cells into irradiated mice. Researchers also sliced off skin from the scalp of the aborted babies and then grafted the fetal skin onto the mice. In the words of the scientists: Full-thickness human fetal skin was processed via removal of excess fat tissues attached to the subcutaneous layer of the skin, then engrafted over the rib cage, where the mouse skin was previously excised.

The body parts used for these experiments were harvested from aborted human fetuses with a gestational age of 18-20 weeks. By that age, an unborn baby hasbrain wavesand abeating heart. He canhear sounds and move his limbs and eyes, and his digestion system has started to work.In other words, the human fetuses whose organs were harvested for this NIH-funded research were well-developed tiny humans, not blobs of undifferentiated cells.

In August, an additional project funded by the NIH came to light thanks to documents obtained in a Freedom of Information Act lawsuit by Judicial Watch and the Center for Medical Progress. The lawsuit was filed after Collinss NIH dragged its feet in responding.According to Judicial Watch, the documents show that theNIH has provided nearly $3 million in tax dollars to support a fetal organ harvesting operation by the University of Pittsburgh in its quest to become a Tissue Hub for human fetal tissue ranging from 6 to 42 [!] weeks gestation.

David Daleiden, president of the Center for Medical Progress,commented: The NIH grant application for just one of Pitts numerous experiments with aborted infants reads like an episode ofAmerican Horror Story. Infants in the womb, some old enough to be viable, are being aborted alive and killed for organ harvesting, in order to bring in millions of dollars in taxpayer funding.

Daleiden furtherallegedthat NIH funding was used to underwrite labor induction abortions, where the baby is pushed out of the mother whole and then killed to obtain the desired tissues. In other words, the NIH was facilitating a process where babies, some of the age of viability, [are] to be delivered alive, and then killing them by cutting their kidneys out.

Francis Collins self-identifies as an evangelical Christian, and most evangelicals as well as faithful Catholics regard abortion as the destruction of innocent human life.

So how has Collins responded to these revelations? With horror? With a pledge to investigate? With a promise to stop taxpayer funding of such research?

Since early August, Ive repeatedly tried to get Collins to answer questions about these NIH funded experiments using aborted fetal organs and tissues.Does Collins support this research funded by his agency? Does he have any ethical objections to it? How does he personally justify the research given his religious convictions? I repeatedly emailed these and other questions to the media contacts for the NIH Office of the Director.

The response? His office has refused to answer.

But its not just NIH research involving humans that has been raising controversy this year. In recent months, Collinss NIH has come under fire for fundingabusive medical experiments on dogsthat critics say were unnecessary as well as barbaric. The experiments were funded by the NIH division headed by Anthony Fauci, but that division is under the ultimate oversight of Collins. In late August, 15 members of Congresssent a letterraising questions about the research.

Again, I tried to get a response from Collins about this latest controversy. Again, he refused to respond to questions.

Ironically, while Collins is AWOL when it comes to answering basic questions about the research his agency is funding, he is more than willing to speak out on other topics, especially COVID-19, where he is now becoming a polarizing figure to many because ofincreasingly shrill advocacy of compulsory vaccination as well as his demonization of those who choose not to take a COVID-19 vaccine.

At the end of April,Collins claimedthat he would not require NIH employees to get vaccinated, and he seemed to argue for a positive approach of selling the benefits of vaccines rather than demonizing the unvaccinated or engaging in finger-wagging. Yet by early August his public posture had changed. He was nowcheerleading for compulsory vaccine requirementsimposed by private businesses as well as enthusiastically overseeing compulsory vaccinations for the very workers at the NIH that he earlier said would not face compulsory vaccination.

After President Bidens speech in September declaringwar on the unvaccinated, Collins ramped up his own rhetoric.In an appearance on MSNBC after Bidens speech, Collins firstsuggestedunvaccinated people were selfish, declaring that this is really an occasion to think about loving your neighbor, not just yourself.

Collins then branded both unvaccinated people and politicians who dont favor vaccine mandates as killers on the wrong side of history. Dismissing their views as merely a philosophical political argument that is part of the culture war, Collins complained that this philosophical political argument is killing people, including, Im sad to say, some children. We have to get past this if we really have a future as a nation.

I would like to say particularly to those leaders who are on the wrong side of this, what Lincoln said one time, Collins declared. Citizens, we will not escape history. Do you want to be looked at in the lens of that backward look ten years from now and defend what you did when in fact, we are losing tens of thousands of lives that didnt have to die?

A question for Collins: Is attacking your fellow citizens (including many fellow Christians) as heartless killers because they disagree with you on either vaccinations or vaccine mandates an example of loving your neighbor?

Whatever one thinks about COVID-19 vaccinations, Collinss over-the-top rhetoric demonizing those he disagrees with as killers is beyond the pale, especially for someone who wears his Christianity on his sleeve. As I have writtenelsewhere, his rhetoric is also based on several falsehoods.

So just how far is Collins willing to go to push coercive medicine? Thats an interesting question.

In my home state of Washington, the governor has issuedan emergency orderthat will compel private religious schools and day care centers as well as other private businesses to fire employees later this month if they wont get vaccinated. While there technically is a route for religious exemptions, it is so narrow and onerous that many religious people may not qualify.

Its now being suggested in some states that discharged employeeswont be able to get unemployment benefits. Perhaps the idea is that if the unvaccinated dont die of COVID they can die of starvation instead.

As if that werent bad enough, the unvaccinated face the denial of medical care. Also in my home state, the University of Washington medical system is now apparently denyingorgan transplantsto patients who are unvaccinated, even if those patients have a credible medical reason for not having the vaccinations.

This is pure, unadulterated social Darwinism: Brand a whole class of people as biologically unfit (in this case, the unvaccinated) and then make sure they cant receive medical care, hold jobs, or basically survive. Heap scorn on them, demonize them as killers, and stir up hatred against them so other people begin to abuse them. If Collins is truly concerned about the judgment of history, he should read a little more widely about the sorry results of demonizing entire classes of people as the enemies of society.

Let me be clear: I am not arguing here about whether people ought to get COVID-19 vaccinations, or whether those vaccinations are helpful. For the record, depending on ones risk profile, I think vaccinations are in a persons best interest. The issue is whether in the name of vaccination people should be stripped of their livelihoods, denied medical care, and demonized as enemies of society. In any morally sane universe, the policies being proposed are as immoral as they are unprecedented.

So does Francis Collins endorse depriving unvaccinated people of their right to work and to support their families? Does he endorse denying them unemployment insurance? Does he go even further and endorse denying medical care to the unvaccinated?

I again asked Collins media relations staff for answers. Again, crickets.

Although Collins likes to tout his personal faith, he appears to have very little concern for any sort of conscience rights of fellows religious believers who disagree with him.After all, he dutifully served in a previous administration that repeatedly weakenedconscience protectionsfor medical workers opposed to abortion and thatviolated federal lawby turning a blind eye when California mandated abortion coverage in all private insurance plans.

It might also be noted that as late as December 2020, Collins was still urging thatmost churches should not meet in person, even implying that they shouldnt do sountil the summer or fall of 2021.

And his current promotion of compulsory vaccinations seemingly has no qualifiers. At least, he isnt talking about any.

Collins hasconcededthat various COVID-19 vaccines used cell lines originally derived from an aborted fetus in either their production or testing, which is one reason some people have moral qualms about the vaccines. Yet you wont find Collins advocating for the conscience rights of these people. In fact, Collins has been silent in the face of attacks on religious exemptions for vaccines.

Reasonable people can disagree about whether the use of abortion-derived cell lines is a moral deal-killer for the vaccines. But thats the point: Reasonable people candisagreeabout what violates their conscience. The test of support for religious liberty is not whether you only support the right of people who agree with you.

Not being willing to stand up for the conscience rights of others to determine their own medical treatment is not morally neutral. It is a moral failure. In the words of theCatholic Bishops of Colorado, A person is morally required to obey his or her conscience, and others should respect the right of others to follow their conscience.

Alas, for those who have followed Francis Collins closely over the years, his current failures of moral leadership come as no surprise. As I will discuss in an upcoming article, Collinss career has been one long testament to moral cowardice and confusion.

Follow this link:
The Appalling Moral Failure of Francis Collins - Discovery Institute

Skin Stem Cells Comments Off on The Appalling Moral Failure of Francis Collins – Discovery Institute | October 5th, 2021

Introduction

The growing burden of ischemic heart disease (IHD) is a major public health issue. The most harmful type of IHD is acute myocardial infarction (MI), which leads to loss of tissue and impaired cardiac performance, accounting for two in five deaths in China.1 Timely revascularization after MI, including percutaneous coronary intervention, thrombolytic treatment and bypass surgery, is key to improving cardiac function and preventing post-infarction pathophysiological remodeling.2 However, these effective but invasive approaches cannot be used in all patients owing to their applicability, which is limited based on specific clinical characteristics, and the possibility of severe complications such as bleeding and reperfusion injury.2,3 Attempts to limit infarct size and improve prognosis using pharmacotherapy (including antiplatelet and antiarrhythmic drugs and angiotensin-converting enzyme inhibitors) without reperfusion has been proven generally inefficient, due to non-targeted drug distribution and side effects, and short half-life of some drugs.1,3,4 Consequently, many patients in which this approach is used still progress to cardiac hypertrophy and heart failure.1 Growth and rupture of atherosclerotic plaques and the ensuing thrombosis are the major causes of acute MI.4 Currently available interventions for atherosclerosis (AS) including statins can reduce acute MI, but the effects vary between individuals, and leave significant residual risks.58 Some chemotherapies, such as docetaxel9 and methotrexate,10,11 also seem to have beneficial effects in AS; however, systemic administration of these drugs is limited because of their adverse effects.12 The demand for safer and more efficient therapies and prevention strategies for MI is therefore increasing.

Several optimized strategies have so far been explored, one of which is the application of nanoparticles (NPs). These nanoscale particles have been widely used in the treatment of tumors and neural diseases.13,14 NPs enable delivery of therapeutic compounds to target sites with high spatial and temporal resolution, enhancement of tissue engineering processes and regulation of the behaviour of transplants such as stem cells. The application of NPs improves the therapeutic effects and minimizes the adverse effects of traditional or novel therapies, increasing the likelihood that they can be successfully translated to clinical settings.1518 However, research on NPs in this field is still in its infancy.5,1921 This review summarizes the latest NP-based strategies for managing acute MI, mostly published within the past 7 years, with a particular focus on effects and mechanisms rather than particle types, which have been extensively covered in other reviews (Figure 1). In addition, we offer an initial viewpoint on the value of function-based systems over those based on materials, and discuss future prospects in this field.

Figure 1 Overview of nanoparticle-based strategies for the treatment and prevention of myocardial infarction. Nanoparticles are capable of delivering therapeutic agents and nucleic acids in a stable and targeted manner, improving the properties of tissue engineering scaffolds, labeling transplanted cells and regulating cell behaviors, thus promoting the cardioprotective effects of traditional or novel therapies.

A multitude of NP types are currently under investigation, including lipid-based NPs, polymeric NPs, micelles, inorganic NPs, and exosomes. Virus can also be considered as NPs; however they will not be discussed in this review.22 NPs made from different materials show similar in vivo metabolic kinetic characteristics and protective effects on infarcted heart.19,20 Function-based NP types, oriented towards a specific purpose, may be preferable compared with traditional types, on account of their practicality in basic research and clinical translation. In this review, we discuss NPs used in the treatment and prevention of MI that fall into the following four categories: 1) circulation-stable nanocarriers (polymeric, lipid or inorganic particles); 2) targeted delivery vectors (magnetic or particles modified to improve target specificity); 3) enhancers of tissue engineering; and 4) regulators of cell behavior (Figure 1). We propose that the choice of each NP for any given application should be primarily based on the roles or mechanisms they perform.

Many NPs, whether composed of either naturally occurring or synthetic materials, act as nanocarriers to improve the circulating stability of therapeutic agents.15,16 Polymeric NPs comprise one of the most widely employed types, with excellent biocompatibility, tunable mechanical properties, and the ability be easily modified with therapeutic agents using a broad range of chemical techniques.23,24 The most commonly used polymer for these NPs is polylactide-co-glycolide (PLGA), which has Food and Drug Administration approval.25,26 Recently, there has been a therapeutic emphasis on polydopamine (PDA), from which several related nanomaterials have been created, including PDA NPs and PDA NP-knotted hydrogels.27,28 NPs made from polylactic acid (PLA),29,30 poly--caprolactone (PCL),31 polyoxalates,32 polyacrylonitrile,33 chitosan29,34 and hollow mesoporous organosilica35 have also been constructed and administered in vitro in cells and in vivo in animal models.

Lipid NPs or liposomes are also considered promising candidates for the delivery of therapeutic agents, due to their morphology, which is similar to that of cellular membranes and ability to carry both lipophilic and hydrophilic drugs. These non-toxic, non-immunogenic and biodegradable amphipathic nanocarriers can be designed to reduce capture by reticuloendothelial cells, increase circulation time, and achieve satisfactory targeting.36,37 Solid lipid NPs (SLNs) combine the advantages of polymeric NPs, fat emulsions, and liposomes, remaining in a solid state at room temperature. Active key components of SLNs are mainly physiological lipids, dispersed in aqueous solution containing a stabilizer (surfactant).38 Micelles are made by colloidal aggregation in a solution through self-assembly of amphiphilic polymers, or a simple lipidic layer of transfer vehicles;39 these have been used in cellular and molecular imaging40 and treatment41 for a long time.

Inorganic NPs used in basic IHD research are classified as metal, metal compounds, carbon,42 or silicon NPs;43 these are relatively inert, stable, and biocompatible. Gold (Au),44 silver (Ag)45 and copper (Cu)46 are commonly used materials in their production. These NPs can be delivered orally,47 or injected intravenously48 or intraperitoneally.56 However, they are more widely used to construct electrically conductive myocardial scaffolds in tissue engineering.49,50 Myocardial patches and scaffolds are promising therapeutic approaches to repairing heart tissue after IHD; incorporating conductive NPs can further improve functionality, introducing beneficial physical properties and electroconductivity. Some organic particles, such as liposomes anchored with poly(N-isopropylacrylamide)-based copolymer groups, are also suitable for the production of effective nanogels or patches for this purpose.37

Several metal compounds have been used for treatment of IHD.5154 The application of magnetic particles made from iron oxide has been of particular interest in recent research. These NPs are more prone to manipulation with an external magnetic field, and thus serve as powerful tools for targeted delivery of therapeutics. In addition, modification with targeted peptides or antibodies is another approach to the construction of targeted delivery systems.

Another strategy to protect cardiac performance after MI is the transplantation of cells; however, the beneficial effects of this are currently limited.58 Many NPs can improve the behavior of cells; in this context, they may stimulate cardioprotective potential. In particular, exosomes a major subgroup of extracellular vesicles (EVs) with a diameter of 30150nm, which are secreted via exocytosis55 represent novel, heterogeneous, biological NPs with an endogenous origin. They are able to carry a variety of proteins, lipids, nucleic acids, and other bioactive substances.5557 Mechanistic studies have confirmed that exosomes offer a cell-free strategy to rescue ischemic cardiomyocytes (CMs).59,60

The physical properties of NPs, including size, shape, and surface charge, impact on how biological processes behave, and consequently, responses in the body.61 The recommended definition of NPs in pharmaceutical technology and biomedicine includes a limitation that more than 50% of particles should be in a size distribution range of 10100 nm.39 However, this is not strictly distinguished in studies, so for the purposes of this review, we have relaxed this definition. Small NPs have a faster uptake and processing speed and longer blood circulation half-lives than larger ones; a decreased surface area results in increased reactivity to the microenvironment and greater speed of release of the compounds they carry.6163 However, an exception to this principle is that, among particles of less than 50 nm diameter, larger NPs have longer circulatory half-lives.64,65 NPs can be spherical, discoidal, tubular or dendritic.61,63 The impact of NP shape on uptake and clearance has also been revealed;66,67 for instance, spheres endocytose more easily,20 while micelles and filomicelles target aortic macrophages, B cells, and natural killer (NK) cells in the immune system more effectively than polymersomes.68 In terms of charge, cationic NPs are more likely to interact with cells than negatively charged or neutral particles because the mammalian cell membrane is negatively charged.62 As a result, positively charged particles are reported to be more likely to destabilize blood cell membranes and cause cell lysis.61 Additionally, the rate of drug release is largely determined by the diameter of the pore. Motivated by the idea, Palma-Chavez et al developed a multistage delivery system by encapsulating PLGA NPs in micron-sized PLGA outer shells.69

Some types of NPs, such as micelles, possess coreshell morphological structures: a core composed of hydrophobic block segments is surrounded by hydrophilic polymer blocks in a shell that stabilizes the entire micelle. The core provides enough space to accommodate compounds, while the shell protects drug molecules from hydrolysis and enzymatic degradation.36 Surface chemical composition largely governs the chemical interactions between NPs and molecules in the body. Appropriate surface coatings can create a defensive layer, protect encapsulated cargo, and affect biological behaviors. Coating with inert polymers like polyethylene glycol (PEG) is the most commonly used method, which hinders interactions with proteins, alters the composition of the protein corona, attenuate NP recognition by opsonins which tag particles for phagocytosis, and extend the half-life of particles.36,70 Additionally, PEG coating helps the therapeutic agents reach ischemic sites, because PEGylated macromolecules tend to diffuse in the interstitial space of the heart.71 Functionalization of gangliosides can further attenuate the immunogenicity of PEGylated liposomes without damaging therapeutic efficacy.72 Removal of detachable PEG conjugates in the microenvironment of the target sites improves capture by cells. Wang and colleagues synthesized PDA-coated tanshinone IIA NPs by spontaneous hydrophobic self-assembly.73 Polyethyleneimine (PEI) is capable of condensing nucleic acid and overcoming hamper of cell membrane. Therefore, modification with PEI is mainly used for the transport of DNA and RNA.74 Of note, despite their inertness, novel NPs composed of metals can also be modified with compounds such as PEG, thiols, and disulfides.48,75 Hydrogels mixed with peptide-coated Au NPs attain greater viscosity than hydrogels mixed with Au NPs.24

Targeted delivery is a primary goal in the development of nanocarriers. Passive targeting is based on enhanced permeability in ischemic heart tissue, which does not meet the needs of clinical application.76 This fact has prompted work on targeting agent modification and magnetic guidance. Conjugation with specific monoclonal antibodies is a feasible method for delivering drug payloads targeted to ischemic lesions. Copper sulfide (CuS) NPs coupled to antibodies targeting transient receptor potential vanilloid subfamily 1 (TRPV1), permit specific binding to vascular smooth muscle cells (SMCs), and can also act as a switch for photothermal activation of TRPV1 signaling.52 In another study conducted by Liu and colleagues, two types of antibodies, binding CD63 (expressed on the surface of exosomes) or myosin light chain (MLC, expressed on injured CMs) are utilized to allow NPs to capture exosomes and accumulate in ischemic heart tissue. These NPs have a unique structure comprising an ferroferric oxide core and PEG-decorated silica shell, which simultaneously enables magnetic manipulation and molecule conjugation via hydrazone bonds.21 Targeted peptides such as atrial natriuretic peptide (ANP),43 S2P peptide (plague-targeting peptide),77 and stearyl mannose (type 2 macrophage-targeting ligand)16 allow NPs to precisely target atherosclerotic tissue and ischemic heart lesions. Modification with EMMPRIN-binding peptide (AP9) has been shown to enable more rapid uptake of micelles by H9C2 myoblasts and primary CMs and to deliver drug payloads targeted to lesions in vivo.78,79 Another strategy for targeted nanocarriers is to produce cell mimetic carriers. Using the inflammatory response as a marker after MI,76 Boada and colleagues synthesized biomimetic NPs (leukosomes) by integrating membrane proteins purified from activated J774 macrophages into the phospholipid bilayer of NPs. Local chronic inflammatory lesions demonstrated overexpression of adhesion molecules, which bound leukosomes efficiently.80

The biocompatibility of NPs is difficult to predict because any interaction with molecules or cells can cause toxic effects. Generally, NPs remain in blood, but can also extravasate from vasculature with enhanced permeability, or accumulate in the mononuclear phagocyte system.81 Important causes of NP-associated toxicity include: oxidative stress injury and cell apoptosis secondary to the production of free radicals, lack of anti-oxidants, phagocytic cell responses, and the composition of some types of particles.61 Hepatotoxicity, nephrotoxicity and any other potential off-target organ damage caused by accumulation of particles, especially those with poor degradability and slow clearance, are also essential to explore in toxicity tests.82 Additionally, the evaluation of evoked immune responses according to the expression of inflammatory factors and stimulation of leukocytes in cell lines and animal models is also important.83

A few studies have reported NP-associated acute and chronic hazards in pharmacological applications, although some of these observations may be contentious. Specifically, aggregation of non-functionalized carbon nanotubes (CNTs) has been observed owing to inherent hydrophobicity of these particles.61 Aside from inflammation and T lymphocyte apoptosis, multi-walled CNTs can rupture cell membranes, resulting in macrophage cytotoxic effects.84,85 Silica NPs induce vascular endothelial dysfunction and promoted the release of proinflammatory and procoagulant factors, mediated by miR-451a negative regulation of the interleukin 6 receptor/signal transducer and activator of transcription/transcription factor (IL6R/STAT/TF) signaling pathway.8688 Metal NPs, such as Au and Ag, can also penetrate the cell membrane, increase oxidative stress and decrease cell viability.89,90 Consequently, exposure to Au may cause nephrotoxicity91 and reversible cardiac hypertrophy.92 El-Hussainy and colleagues observed myocardial dysfunction in rats given alumina NPs.93,94 Nemmar and colleagues investigated the toxicity of ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) administered intravenously, which resulted in cardiac oxidative stress and DNA damage as well as thrombosis.95 Cell-derived exosomes and a majority of natural polymers are considered relatively safe;83 however, Babiker and colleagues demonstrated that dendritic polyamidoamine NPs compromise recovery from ischemia/reperfusion (I/R) injury in isolated rat hearts.96 The effects of degradation byproducts are also of concern.83 An advantage of the nanoscale size of NPs is that their injection is unlikely to block the microvascular system; however, it remains controversial whether NPs give rise to arrhythmias.97 These factors highlight that examining the biocompatibility of NPs both in vitro and in vivo is a vital component of preclinical or clinical research.

NP toxicity depends on many parameters, including material composition, coating, size, shape, surface charges and concentration.39 For instance, larger particles seem to be more favorable from a toxicology standpoint.83 However, single-walled CNTs are considered more harmful than multi-walled CNTs, due to their smaller size resulting in less aggregation and increased uptake by macrophages.61 Cationic AuNPs are more toxic compared with anionic AuNPs, which appear to be nontoxic.98 Generally speaking, NP-associated toxicity can be lowered by functionalization with nontoxic surface molecules, stabilization and localization in the region of interest by using scaffolds.24,99 The toxicity of CNTs mediated by oxidative stress and inflammation was reduced using these strategies in several studies.24,100 Local application and targeted delivery also enabled dose reduction and concurrently decreased the incidence of adverse effects. Administration of therapeutic agents directly into the infarcted or peri-infarcted myocardium is a conventional approach with a low risk of inducing embolization.

NP is a suitable method for the administration of therapeutic agents in terms of the minimization of side effects, enhanced stability of cargo, and possibility of controlled delivery and release.76 Detailed information on the experimental design and results of the latest studies on the use of NPs as therapeutic vectors are provided in Table 1. Recently, several drugs approved for clinical use as immunosuppressants have been suggested as potentially effective cardioprotective agents. For example, NPs containing cyclosporine A inhibited apoptosis and inflammation in ischemic myocardium by improving mitochondrial function.25,101 Commercial methotrexate also showed minor cardioprotective effects; additionally, when loaded into lipid core NPs, adenosine bioavailability and echocardiographic and morphometric results were all improved a rats model of MI.102 Margulis and colleagues developed a method to fabricate NPs via a supercritical fluids setup, which loaded and transferred celecoxib, a lipophilic nonsteroidal anti-inflammatory drug, into the NPs. These celecoxib-containing NPs alleviated ejection function damage and ventricular dilation by inducing significant levels of neovascularization.103 Furthermore, a series of investigations indicated that drugs used for hypoglycemia (eg pioglitazone, exenatide and liraglutide)104106 and lipid lowering (statins)107 attenuate the progression of post-MI heart failure, and are therefore also potential therapeutic cargoes for NPs in the treatment of MI.

NP systems also offer an alternative method for delivering plant-derived therapeutic agents, most of which belong to traditional Chinese medicine. Its of vital importance because of the criticization on adverse reactions caused by direct injection of such complexes. Cheng and colleagues designed a dual-shell polymeric NP as a multistage, continuous, targeted vehicle of resveratrol, a reactive oxygen species (ROS) scavenger. Due to the severe oxide stress in areas of infarction, the proposed antioxidant-delivery NPs represent a new method to effectively treat MI. These NPs are modified with two peptides, targeting ischemic myocardium and mitochondria, respectively; cardioprotective effects have been confirmed in both hypoxia/reoxygenated (H/R) H9C2 cells and I/R rats.108 In addition, Dong and colleagues also demonstrated that puerarin-SLNs produced smaller areas of infarction in a MI rat model, evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. These particles were modified with cyclic arginyl-glycyl-aspartic acid peptide, a specific targeting moiety to v3 integrin receptors, which are highly expressed on endothelial cells (ECs) during angiogenesis.109 In a recent study, quercetin was loaded into mesoporous silica NPs, which enhanced the inhibition of cell apoptosis and oxidative stress, improving ventricular remodeling and promoting the recovery of cardiac function by activating the janus kinase 2 (JAK2)/STAT3 pathway.110 Similarly, curcuminpolymer NPs, administered by gavage, improved serum inflammatory cytokine levels compared with direct administration of curcumin.111

Translation of novel bioactive agents into clinical practice has been limited, owing to lack of sufficient bioavailability and systemic toxicity.76 Encapsulating small molecules such as 3i-1000 (an inhibitor of the GATA4NKX2-5 interaction),43 TAK-242 (inhibitor of toll-like receptor 4, TLR4)112 and C143 (inhibitor of ERK1/2)113 in NPs promotes myocardial repair after MI without the risk of uncontrolled and off-target adverse effects. Administration of vascular endothelial growth factor (VEGF) causes elevated vascular permeability and tissue edema. The cardioprotective effects of VEGF-loaded polymeric NPs injected either intravenously114 or intramyocardially115 eliminated vascular leakage due to promotion of lymphangiogenesis. Further studies have confirmed these results and add to the evidence that combined delivery of VEGF with other growth factors is recommended, since VEGF primarily drives the formation of new capillaries.116 Furthermore, in line with previous research, similar therapeutic effects have been demonstrated in studies using polymeric NPs loaded with stromal cell derived factor 1 (SDF-1) and insulin-like growth factor 1 (IGF-1).117,118

We also notice that some novel payloads in NPs-based therapy for MI have been studied. For example, deoxyribozyme-AuNP can silence tumor necrosis factor- (TNF-).119 A target that is implicated in irreversible heart damage after MI; its effects are mediated by free radical production, downregulation of contractile proteins, and initiation of pro-inflammatory cytokine cascades. Mesoporous iron oxide NPs containing the hydrogen sulfide donor compound diallyl trisulfide act as a platform for the controlled and sustained release of this therapeutic gas molecule. The application of these NPs at appropriate concentrations, resulted in the preservation of cardiac systolic performance without any observable detrimental effects on homeostasis in vivo.15

With increasing insight into the molecular mechanisms of MI, a particular emphasis on gene therapy has emerged. Gene expression can be modulated by DNA fragments, messenger RNA (mRNA), microRNA (miRNA) and small interfering RNA (siRNA), which thus represent new approaches for treating ischemia. Currently available nucleic acid delivery systems are mainly divided into viral and non-viral systems. However, virus-based approaches are limited by their potential for uncontrollable mutagenesis.36 From a clinical point of view, NP represents a suitable choice as novel non-viral nucleic acid vector, which could feasibly transfect in a stable, targeted, and sustained manner (as shown in Table 2).

Table 2 NPs-Based Nucleic Acid Delivery Systems for Treatment for MI Reported in the Last 7 Years

As a common gene vehicle, plasmids face the risk of being destroyed by DNase and immunoreactivity in the serum, and transduction in non-target organs.120 A recent study by Kim and colleagues aligns with current research trends focused on virus-free therapies, in which carboxymethylcellulose NPs were designed to transfer 5-azacytidine to halt proliferation, and deliver plasmid DNA containing GATA4, myocyte enhancer factor 2C (MEF2C), and TBX5 to induce reprogramming and cardiogenesis of mature normal human dermal fibroblasts.121 In a methodological study, lipidoid NPs were used to successfully deliver pseudouridine-modified mRNA, encoding enhanced green fluorescent protein.122

MiRNAs act as essential regulators of cellular processes through post-transcriptional suppression; increasing evidence reveals miRNAs play critical roles in cardiovascular diseases. An miRNA-transferring platform with self-accelerating nucleic acid release, containing a heparin core and an ethanolamine-modified poly(glycidyl methacrylate) shell, has been constructed and used as an efficient vector of miR-499, which inhibits cardiomyocyte apoptosis.123 Intravenous administration of anionic hyaluronan-sulfate NPs (mean diameter 130 nm) enable the stable delivery of miR-21 mimics, thus modulating the expression of TNF, transforming growth factor (TGF), and suppressor of cytokine signaling 1 (SOCS1). Consequently, these NPs switch the phenotype of macrophages from pro-inflammatory to reparative, promote neovascularization and reduced collagen deposition.124 Interestingly, silencing miR-21 using antagomiR-21a-5p in a nanoparticle formulation has also been shown to reduce expression of pro-inflammatory cytokines in vitro, and attenuate inflammation and fibrosis in mice with autoimmune myocarditis.125 A number of other potentially therapeutic miRNAs have also been successfully transferred to CMs in recent works, including miR-146a, miR-146b-5p, miR-181b, miR-199-3p, miR-214-3p, miR-194-5p and miR-122-5p.126128 Evaluation of angiogenesis, cardiac function, and scar size in these studies indicated that injectable miRNANPs can deliver miRNA to restore injured myocardium efficiently and safely. Yang and colleagues developed an in vivo miRNA delivery system incorporating a shear-thinning hydrogel and NPs characterized by surface presence of miRNA and cell-penetrating peptide (CPP).126 Additionally, angiotensin II type 1 receptor-targeting peptide-modified NPs serve as targeted carriers for anti-miR-1 antisense oligonucleotide, significantly reducing apoptosis and infarct size.129

SiRNAs inhibit gene expression by mediating mRNA cleavage in a sequence-specific manner, highlighting NP-based RNA interference as another viable approach to modulate cellular phenotype and attenuate cardiac failure. Dosta and colleagues demonstrated that poly(-amino ester) particles modified by adding lysine-/histidine-oligopeptides could represent a system for the transfer of siRNA.130 Studies have now revealed that chemokine CC motif ligand 2 (CCL2) and its cognate receptor CC chemokine receptor 2 (CCR2) promoted excessive Ly6Chigh inflammatory monocyte infiltration in infarcted area and aggravate myocardial injury.131 Photoluminescent mesoporous silicon nanoparticles (MSNPs) carrying siCCR2 have been reported to improve the effectiveness of transplanted mesenchymal stem cells (MSCs) in reducing myocardial remodeling after acute MI.131 Targeted transportation and enhanced uptake with minimum leakage improved the efficiency of delivery via NPs, significantly outperforming the control group. Taken together, these studies demonstrate that NPs act as promising drug delivery systems in the treatment of MI.

Myocardial patches and scaffolds, consisting of either bioactive hydrogels or nanofibers, are minimally invasive, relatively localized, and targeted approaches to repair the heart after IHD. Those biomaterials must have an anisotropic structure, mechanical elasticity, electrical conductivity, and the ability to promote ischemic heart repair.132 A variety of NPs have been applied in this field, among which inorganic NPs have been the focus of most research efforts.42 These investigations of inorganic NPs can be divided into four categories based on their effects and the mechanisms involved, which are described in this section.

NPs enhance physical properties and electroconductivity, which is essential for the biomaterials to properly accommodate cardiac cells and subsequently resulted in cell retention, cell-cell coupling and robust synchronized beating behavior. CNTs are able to increase the required physical properties of scaffolds, such as maximum load, elastic modulus, and toughness.133,134 Gelatin methacrylate (GelMA) also has decreased impedance, hydrogel swelling ratio, and pore diameter, as well as increased Youngs modulus when combined with gold nanorods (AuNRs).135 Given this insight, highly electroconductive NPs have been increasingly investigated.34,99 Specifically, Ahadian and colleagues revealed that a higher integrated CNT concentration in gels resulted in greater conductivity.136 Zhou and colleagues verified the therapeutic effects of patches incorporating single-walled CNT for myocardial ischemia, which halted progressive cardiac dysfunction and regenerated the infarcted myocardium.137 Spherical AuNPs have also been shown to increase the conductivity of chitosan hydrogels in a concentration-dependent manner.138 Interestingly, silicon NPs mimic the effects of AuNRs without affecting conductivity or stiffness, as reported by Navaei and colleagues.139

Several studies demonstrate the effects of CNT on CM functions. When CMs are cultured on multi-walled CNT substrates or treated with CNT-integrated patches, these cells show spontaneous electrical activity.34,99,140 Brisa and colleagues functionalized reverse thermal gels with AuNPs, investigating the phenotype of CMs in vitro; the growth of cells with a CM phenotype was observed, along with gap junction formation.141 CMs exposed to AuNR-containing GelMa show higher affinity, leading to packed and uniform tissue structure.135 These conductive scaffolds also facilitate the robustness and synchrony of spontaneous beating in CMs without damaging their viability and metabolic activity.

Combined incorporation of inorganic NPs and cells represents a feasible strategy to promote therapeutic effects. Despite some reports on the cytotoxicity of Au,89,90 no significant loss of viability, metabolism, migration, or proliferation of MSCs in scaffolds containing AuNP is reported. A CNT-embedded, electrospun chitosan/polyvinyl alcohol mesh is reported to promote the differentiation of MSCs to CMs.142 In another approach, Baei and colleagues added AuNPs to chitosan thermosensitive hydrogels seeded with MSCs.138 There was a significant increase in expression of early and mature cardiac markers, indicating enhanced cardiomyogenic differentiation of MSCs compared to the matrix alone, while no difference in growth was observed. Gao et al created a fibrin scaffold, in which cells and AuNPs were suspended simultaneously; these bioactive patches were shown to promote left ventricular function and decrease infarct size and apoptosis in the periscar boarder zone myocardium in swine models of acute MI.97 These studies of AuNP-containing scaffolds demonstrated reduced infarct and fibrotic size, as well as facilitated angiogenesis and cardiac function, which can be attributed at least in part to the enhanced expression of connexin 43 and atrial natriuretic peptide, and activation of the integrin-linked kinase(ILK)/serine-threonine kinase (p-AKT)/GATA4 pathway.49,143,144 Scaffolds containing Ag NPs evoke M2 polarization of macrophages in vitro;145 which may also play a role in cardioprotective action because M2 macrophages are capable of promoting cardiac recovery via the secretion of anti-inflammatory cytokines, collagen deposition, and neovascularization.146

Similarly, CNT also act synergically with poly(N-isopropylacrylamide) scaffolds containing adipose-derived stem cells;147 significant improvement of cardiac function and increased implantation and proliferation of stem cells has been observed with these scaffolds, compared with scaffolds without CNT.147 Selenium NPs148 and titania NPs53 have been shown to improve the mechanical and conductive properties of chitosan patches, promoting their ability to support proliferation and the synchronous activity of cells growing on these patches.

Mounting evidence demonstrates the unique benefits of using cardiac scaffolds with magnetic NPs such as SPIONs; these benefits include, but are not limited to, significant improvements in cell proliferation149 and assembly of electrochemical junctions.150 Given that magnetic manipulation enhances the therapeutic efficacy of iron oxide NPs in cardiac scaffolds, Chouhan and colleagues designed a magnetic actuator device by incorporating magnetic iron oxide NPs (MIONs) in silk nanofibers; this resulted in more controlled drug release properties, as well as the promotion of proliferation and maturation in CMs.151 Magnetic NPs can be used to label induced pluripotent stem cell (iPSC)-derived CMs via conjugation with antibodies against signal-regulatory protein . Zwi-Dantsis and colleagues reported the construction of tailored cardiac tissue microstructures, achieved by orienting MION-labelled cells along the applied field to impart different shapes without any mechanical support.152 However, the interactions between and effects of NPs and cells in scaffolds, and the cardioprotective efficacy of patches in which NP-labelled cells are suspended, require further elucidation.

Polymeric nanomaterials have also been investigated in the context of cardiac bioengineering materials; for instance, water-swollen polymer NPs have been used to prepare nanogels. With a 3D structure containing cross-linked biopolymer networks, nanogels can encapsulate, protect, and deliver various agents.83,153 PDA-coated tanshinone IIA NPs suspended in a ROS-sensitive, injectable hydrogel via PDA-thiol bonds significantly improved cardiac performance, accompanied by inhibition of the expression of inflammation factors in rat model.73 After implanting cryogel patches consisting of GelMa and linked conductive polypyrrole NPs154 or scaffolds of electrospun GelMA/polycaprolactone with GelMA-polypyrrole NPs,155 left ventricular (LV) ejection fraction (EF) has been shown to increase, with a concurrent decrease in infarct size, in MI animal models.

Progenitor or stem cell-based therapy in the form of injections and engineered cardiac patches, discussed in the previous section, has been recognized as a promising strategy to improve the cardiac niche and ameliorate adverse remodeling processes and fibrosis after acute MI.56,156,157 However, poor survival and low engraftment rates for transplanted cells are still major challenges in this field.157 Among possible optimization strategies, combining NPs with stem cell therapy is of great interest (Table 3).

Table 3 Studies Combining NPs and Cell Therapy Reported in the Last 7 Years

Accumulating evidence has shown two main mechanisms for NP-loaded cell therapy in the context of MI treatment. Firstly, various NP types could efficiently improve survival and cell proliferation, modulating differentiation of implanted cells in the ischemic microenvironment.62,158 Specifically, electrically driven nanomanipulators could guide cardiomyogenic differentiation of MSCs: in a previous study, electroactuated gold NPs were administrated with pulsed electric field stimulation, and tube-like morphological alterations were observed, along with upregulation of cardiac specific markers.143 Adipose-derived stem cells that load PLGA-simvastatin NPs promoted differentiation of these cells into SMCs and ECs, and had cardioprotective effects in a mouse model of MI induced by left anterior descending ligation.17 Secondly, engraftment rate is another important factor affecting treatment efficacy in this context.159 Zhang and colleagues designed silica-coated, MION-labelled endothelial progenitor cells; intravenous administration of these cells in a rat model of MI significantly improved cardiac performance, as indicated by echocardiogram, morphological, and histological evidence, and neovascularization. This indicates magnetic guidance may potentially address the problem of low levels of stem cell retention, which has typically been observed.51 In particular, NPs can link the therapeutic cells to injured CMs, thereby promoting cell anchorage and engraftment. To this end, Cheng and colleagues established a magnetic, bifunctional cell connector by conjugating NPs with two antibodies: one against cell determinant (CD)45, which is expressed on bone marrow-derived stem cells, and one against MLC. The magnetic core of this NP also enabled physical enrichment in ischemic heart tissue using external magnets.160 More than one mechanism may be involved in a study. Chen and colleagues fabricated a sustained release carrier of insulin-like growth factor (IGF), a pro-survival agent, via in situ growth of Fe3O4 NPs on MSNPs. In this study, the NPs promoted both the survival and retention of MSCs, and intramyocardial injection of the NP-labeled MSCs was able to ameliorate functional and histological damage without any obvious toxicity in vivo.161 However, SPION labeling does not seem to improve therapeutic efficiency, as demonstrated by Wang and colleagues in a study using hypoxia-preconditioned SPION-labeled adipose-derived stem cells (ASCs).162

Primary criticisms of cell-based therapies include their potential immunogenicity, arrhythmogenicity and tumorigenicity. It is widely accepted that the beneficial effects of cell-based therapy are mainly attributable to paracrine effects rather than directly replenishing lost CMs;56 researchers are therefore investigating of cell-free approaches. Exosomes have attractive properties including stable transport, homing to target tissues or cells, and penetration of biological barriers, as well as being more biocompatible with lower immunogenicity than cell-based approaches. Interestingly, post-MI circulating exosomes serve as important cardioprotective messengers.163,164 Manipulating their biodistribution has proven to be a viable strategy to reduce infarct size, promoting angiogenesis and ejection functions.21 However, from a therapeutic standpoint, the lack of control over endogenous exosome production and cargo encapsulation limits the use of this naturally-present mechanism for therapeutic enhancement. The low purity and weak targeting of natural exosomes are two further obstacles to overcome before clinical application. Strategies to address these include finding robust sources; optimized isolation methods for higher yields, efficiency and purity; and improving therapeutic payloads. These have been systematically summarized in other reviews.165167

AS is considered a low-grade, chronic inflammatory disease, characterized by accumulation and deposition of cholesterol in arteries, as well as remodeling of the extracellular matrix in the intima and inner media.12,168 Inflammation of ECs, proliferation of SMCs, and recruitment of monocytes and macrophages play a critical role in the development of AS. NPs allow for the packaging of large amounts of therapeutic compounds in a compact nanostructure, specifically targeting pathological mechanisms and attenuating atherogenesis. Optimization of the loaded drug and NP target together lead to enhanced efficacy while minimizing side effects.169 In this section, we summarize recent breakthroughs in the order of pathological progression, as shown in Table 4.

Primary prevention refers to control of the risk factors of AS, one of which is hypertension.170 PLA NPs have been shown to improve the efficacy of aliskiren, the first oral direct renin inhibitor and the first in a new class of antihypertensive agents.29 Encapsulation in nanocarriers also renders the application of anandamide viable, which was once limited; recent research revealed that this new therapy could lower blood pressure and LV mass index in rats.171 Similar results were observed in a study in which angiotensinogen was silenced using small hairpin RNA.172 NPs may also help to make more anti-hypertensive drugs available, reduce side effects such as asthma, and lessen the effective dosage by providing sustained drug release over time. The link between AS and diabetes mellitus, which describes a group of metabolic disorders, has also been investigated in numerous studies.173 Possible mechanisms include oxidative stress, altered protein kinase signaling, and epigenetic modifications. Cetin and colleagues successfully constructed NP-based drug delivery systems for the administration of metformin, an oral antihyperglycemic agent with low oral bioavailability and short biological half-life.174 NPs are also promising tools for improving the oral bioavailability of insulin, which is of great interest because oral insulin will significantly increase patients compliance.175,176

The inflammatory hypothesis of AS is now widely established, making selective targeting and accumulation of NPs in inflammatory lesions attractive therapeutic strategies. Targeting macrophages in apoE-/- mice has been shown to result in decreased phagocytosis and suppression of inflammatory genes in lesional macrophages, thus lessening burden of atherosclerotic plaques.177 Tom and colleagues used NPs consisting of high-density lipoprotein (HDL), a known atheroprotective bionanomaterial, as carriers for TNF receptor-associated factor in mice, and observed reductions in both leukocyte recruitment and macrophage activation.178 Both single-walled CNT and HDL-NPs have a favorable safety profile. In a pathological context, activated endothelial tissue expresses more adhesion molecules, such as selectins, than usual. These molecules are thus potential targets for cardiovascular nanomedicine. Glycoprotein Ib (GPIb)179 and biotinylated Sialyl Lewis A (sLeA)69 specifically bind to selectins, leading to the accumulation of conjugated NPs in injured vessels; an in vitro study demonstrated that GPIb-conjugated NPs could bind to target surfaces, where they were taken up by activated ECs under shear stress conditions. In another study, Sager and colleagues simultaneously inhibited five adhesion molecules associated with leukocyte recruitment in post-MI apoE-/- mice. Inflammation in plaque and ischemic heart, rendering acute coronary events and post-MI complications less likely to occur.180 However, targeting inflammatory process may have heterogeneous effects in humans because the targeting moieties and target receptors may be overexpressed in several different pathologic conditions in addition to AS. Oxidation is another factor involved in the development of AS. Upregulation of endothelial nitric oxide synthase (eNOS) leads to vascular construction and other AS-promoting effects. Pechanova and colleagues observed that the application of PLA NPs resulted in larger decreases in NOS than direct administration.29

Aside from these processes, avoiding plaque rupture and thrombosis could be another therapeutic aim. Nakashiro and colleagues showed that delivering pioglitazone via NPs inhibited plaque rupture in apoE-/- mice.181 The integrin 3 is upregulated in angiogenic vasculature, which is ubiquitous in plaque ruptures, which may lead to MI.182 3 integrin-targeted NPs provide a site-specific drug delivery platform that has been shown to successfully stabilize plaques in rabbits.182 Ji and colleagues used NPs composed of albumin with an average diameter of 225.6 nm to deliver a plasmid containing the tissue-type plasminogen activator gene (t-PA); this system plays a role in preventing thrombosis in addition to attenuating intimal thickness and proliferation of vascular SMCs.183 NPs consisting of engineered amphipathic cationic peptide and serine/threonine protein kinase JNK2 siRNA also reduces thrombotic risk, plaque necrotic area, and vascular barrier disorder in mice given the equivalent of a 14-week western diet.184

Innovation and development of therapies based on NPs in recent years has led to significant advances towards complete repair of the injured myocardium following acute MI. Nevertheless, developing clinically relevant solutions remains difficult for several reasons. Firstly, as shown in tables, there is little consistency among studies regarding the characteristics of NPs, their payloads, and their methods of administration, as well as methods used for evaluating cardiac repair. It can be difficult to control characteristics such as the size of the synthesized particles in a narrow range, even within single studies. Such significant heterogeneity can lead to differences in observed results in repeated experiments, or under different conditions. Secondly, although many studies have focused on the health effects of unintentional exposure to NPs by inhalation or ingestion,185,186 most of the studies on medical applications of NPs have not reported on toxicity of NP systems until recently.73 Remarkably, there has not been a consensus on NP-associated adverse effects in existing reports, making assessments of biocompatibility a priority for NP characterization.

NPs have emerged as a powerful tool for controlling cell signaling pathways in regenerative strategies using novel therapeutics and drugs that are unsuitable for direct administration. One advantage of the application of NP systems is the ability to release the drug payload or regulate gene expression in a stable and controlled manner. Therefore, many otherwise serious side effects, such as sudden arrhythmic deaths resulting from persistent and uncontrolled expression of miRNA by viral vectors, may be completely avoided.187 More research is required to develop stable and efficient methods of NP production, improve encapsulation efficiency of drugs, and achieve satisfactory targeting. In particular, a greater focus on investigating NP-based switches, including optical, electrical and magnetic methods, has enabled the regulation of cell signaling, exemplified by the development of a CuS NP-based photothermal switch.52 Optimizing tissue engineering scaffolds containing conductive NPs is a promising strategy for the protection of the myocardium after ischemia by mimicking the myocardial extracellular matrix. Improvements in understanding of cardiac repair mechanisms, and how these biomaterials may interfere with them, is therefore urgently needed. Furthermore, heart repair is complex and involves many processes, including apoptosis, angiogenesis, inflammatory infiltration, and fibrosis. Therefore, novel treatments should be designed using NP-based integrative strategies based on these multiple different mechanisms. However, its important to highlight that synergistic effects of different drug payloads, NPs, and NPcell combined strategies should be addressed, as not all may be compatible with one another. Future research should focus on these aspects to translate NP-based therapeutic strategies for MI into practical and effective clinical use.

The authors report no conflicts of interest in this work.

1. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet. 2017;389(10065):197210. doi:10.1016/s0140-6736(16)30677-8

2. Marn-Juez R, El-Sammak H, Helker CSM, et al. Coronary revascularization during heart regeneration is regulated by epicardial and endocardial cues and forms a scaffold for cardiomyocyte repopulation. Dev Cell. 2019;51(4):503515.e4. doi:10.1016/j.devcel.2019.10.019

3. Rentrop KP, Feit F. Reperfusion therapy for acute myocardial infarction: concepts and controversies from inception to acceptance. Am Heart J. 2015;170(5):971980. doi:10.1016/j.ahj.2015.08.005

4. Arbab-Zadeh A, Nakano M, Virmani R, Fuster V. Acute coronary events. Circulation. 2012;125(9):11471156. doi:10.1161/circulationaha.111.047431

5. Ou LC, Zhong S, Ou JS, Tian JW. Application of targeted therapy strategies with nanomedicine delivery for atherosclerosis. Acta Pharmacol Sin. 2021;42(1):1017. doi:10.1038/s41401-020-0436-0

6. Gorabi AM, Kiaie N, Reiner , Carbone F, Montecucco F, Sahebkar A. The therapeutic potential of nanoparticles to reduce inflammation in atherosclerosis. Biomolecules. 2019;9(9):2545. doi:10.3390/biom9090416

7. Young DR, Hivert MF, Alhassan S, et al. Sedentary behavior and cardiovascular morbidity and mortality: a science advisory from the American Heart Association. Circulation. 2016;134(13):e26279. doi:10.1161/cir.0000000000000440

8. Ekroos K, Jnis M, Tarasov K, Hurme R, Laaksonen R. Lipidomics: a tool for studies of atherosclerosis. Curr Atheroscler Rep. 2010;12(4):273281. doi:10.1007/s11883-010-0110-y

9. Meneghini BC, Tavares ER, Guido MC, et al. Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model. Vascul Pharmacol. 2019;115:4654. doi:10.1016/j.vph.2019.02.003

10. Bulgarelli A, Martins Dias AA, Caramelli B, Maranho RC. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. J Cardiovasc Pharmacol. 2012;59(4):308314. doi:10.1097/FJC.0b013e318241c385

11. Cervadoro A, Palomba R, Vergaro G, et al. Targeting inflammation with nanosized drug delivery platforms in cardiovascular diseases: immune cell modulation in atherosclerosis. Front Bioengineering Biotechnol. 2018;6:177. doi:10.3389/fbioe.2018.00177

12. Zhang J, Zu Y, Dhanasekara CS, et al. Detection and treatment of atherosclerosis using nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017;9(1). doi:10.1002/wnan.1412

13. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):21082121. doi:10.1056/NEJMoa1809615

14. Bahadur S, Sachan N, Harwansh RK, Deshmukh R. Nanoparticlized system: promising approach for the management of alzheimers disease through intranasal delivery. Curr Pharm Des. 2020;26(12):13311344. doi:10.2174/1381612826666200311131658

15. Wang W, Liu H, Lu Y, et al. Controlled-releasing hydrogen sulfide donor based on dual-modal iron oxide nanoparticles protects myocardial tissue from ischemia-reperfusion injury. Int J Nanomedicine. 2019;14:875888. doi:10.2147/ijn.S186225

16. Banik B, Surnar B, Askins BW, Banerjee M, Dhar S. Dual-targeted synthetic nanoparticles for cardiovascular diseases. ACS Appl Mater Interfaces. 2020;12(6):68526862. doi:10.1021/acsami.9b19036

17. Yokoyama R, Ii M, Masuda M, et al. Cardiac regeneration by statin-polymer nanoparticle-loaded adipose-derived stem cell therapy in myocardial infarction. Stem Cells Transl Med. 2019;8(10):10551067. doi:10.1002/sctm.18-0244

18. Wang J, Xiang B, Deng J, et al. Externally applied static magnetic field enhances cardiac retention and functional benefit of magnetically iron-labeled adipose-derived stem cells in infarcted hearts. Stem Cells Transl Med. 2016;5(10):13801393. doi:10.5966/sctm.2015-0220

19. Gadde S, Rayner KJ. Nanomedicine Meets microRNA: current Advances in RNA-Based Nanotherapies for Atherosclerosis. ACS Nano. 2016;36(9):e739. doi:10.1161/atvbaha.116.307481

20. Sun Y, Lu Y, Yin L, Liu Z. The roles of nanoparticles in stem cell-based therapy for cardiovascular disease. Int J Nanomedicine. 2020;8:947. doi:10.3389/fbioe.2020.00947

21. Liu S, Chen X, Bao L, et al. Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles. Nat Biomed Eng. 2020;4(11):10631075. doi:10.1038/s41551-020-00637-1

22. Pitek AS, Wang Y, Gulati S, et al. Elongated plant virus-based nanoparticles for enhanced delivery of thrombolytic therapies. Mol Pharm. 2017;14(11):38153823. doi:10.1021/acs.molpharmaceut.7b00559

23. Won YW, McGinn AN, Lee M, Bull DA, Kim SW. Targeted gene delivery to ischemic myocardium by homing peptide-guided polymeric carrier. Article. Mol Pharm. 2013;10(1):378385. doi:10.1021/mp300500y

24. Sink E, Narayan SP, Abdel-Hafiz M, Mestroni L, Pea B. Nanomaterials for cardiac tissue engineering. Molecules. 2020;25(21). doi:10.3390/molecules25215189

25. Zhang CX, Cheng Y, Liu DZ, et al. Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats. J Nanobiotechnology. 2019;17(1):18. doi:10.1186/s12951-019-0451-9

26. Oduk Y, Zhu W, Kannappan R, et al. VEGF nanoparticles repair the heart after myocardial infarction. Am J Physiol Heart Circ Physiol. 2018;314(2):H278h284. doi:10.1152/ajpheart.00471.2017

27. Caldas M, Santos AC, Veiga F, Rebelo R, Reis RL, Correlo VM. Melanin nanoparticles as a promising tool for biomedical applications - a review. Acta biomaterialia. 2020;105:2643. doi:10.1016/j.actbio.2020.01.044

28. Wang X, Wang C, Wang X, Wang Y, Zhang Q, Cheng Y. A polydopamine nanoparticle-knotted poly(ethylene glycol) hydrogel for on-demand drug delivery and chemo-photothermal therapy. Chem Mater. 2017;29(3):13701376. doi:10.1021/acs.chemmater.6b05192

29. Pechanova O, Barta A, Koneracka M, et al. Protective effects of nanoparticle-loaded aliskiren on cardiovascular system in spontaneously hypertensive rats. Molecules. 2019;24(15):2710. doi:10.3390/molecules24152710

30. Mao S, Wang L, Chen P, Lan Y, Guo R, Zhang M. Nanoparticle-mediated delivery of Tanshinone IIA reduces adverse cardiac remodeling following myocardial infarctions in a mice model: role of NF-B pathway. Artif Cells, Nanomed Biotechnol. 2018;46(sup3):S707s716. doi:10.1080/21691401.2018.1508028

31. Guex AG, Kocher FM, Fortunato G, et al. Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development. Acta biomaterialia. 2012;8(4):14811489. doi:10.1016/j.actbio.2011.12.033

32. Bae S, Park M, Kang C, et al. Hydrogen peroxide-responsive nanoparticle reduces myocardial ischemia/reperfusion injury. J Am Heart Assoc. 2016;5(11). doi:10.1161/jaha.116.003697

33. Wu S, Duan B, Qin X, Butcher JT. Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering. Acta biomaterialia. 2017;51:89100. doi:10.1016/j.actbio.2017.01.051

34. Pok S, Vitale F, Eichmann SL, Benavides OM, Pasquali M, Jacot JG. Biocompatible carbon nanotube-chitosan scaffold matching the electrical conductivity of the heart. ACS Nano. 2014;8(10):98229832. doi:10.1021/nn503693h

35. Zhu K, Wu M, Lai H, et al. Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in vivo cardiac repair. Biomaterials. 2016;74:188199. doi:10.1016/j.biomaterials.2015.10.010

36. Singh B, Garg T, Goyal AK, Rath G. Recent advancements in the cardiovascular drug carriers. Artif Cells, Nanomed Biotechnol. 2016;44(1):216225. doi:10.3109/21691401.2014.937868

37. Jung H, Jang MK, Nah JW, Kim YB. Synthesis and Characterization of Thermosensitive Nanoparticles Based on PNIPAAm Core and Chitosan Shell Structure. Article. Macromol Res. 2009;17(4):265270. doi:10.1007/bf03218690

38. Paliwal R, Paliwal SR, Kenwat R, Kurmi BD, Sahu MK. Solid lipid nanoparticles: a review on recent perspectives and patents. Expert Opin Ther Pat. 2020;30(3):179194. doi:10.1080/13543776.2020.1720649

39. Piperigkou Z, Karamanou K, Engin AB, et al. Emerging aspects of nanotoxicology in health and disease: from agriculture and food sector to cancer therapeutics. Food Chem Toxicol. 2016;91:4257. doi:10.1016/j.fct.2016.03.003

40. Chen W, Jarzyna PA, van Tilborg GA, et al. RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe. FASEB j. 2010;24(6):16891699. doi:10.1096/fj.09-139865

41. Nguyen J, Sievers R, Motion JP, Kivime S, Fang Q, Lee RJ. Delivery of lipid micelles into infarcted myocardium using a lipid-linked matrix metalloproteinase targeting peptide. Mol Pharm. 2015;12(4):11501157. doi:10.1021/mp500653y

42. Ashtari K, Nazari H, Ko H, et al. Electrically conductive nanomaterials for cardiac tissue engineering. Adv Drug Deliv Rev. 2019;144:162179. doi:10.1016/j.addr.2019.06.001

43. Kinnunen SM, Tlli M, Vlimki MJ, et al. Cardiac Actions of a Small Molecule Inhibitor Targeting GATA4-NKX2-5 Interaction. Sci Rep. 2018;8(1):4611. doi:10.1038/s41598-018-22830-8

44. Dong Y, Hong M, Dai R, Wu H, Zhu P. Engineered bioactive nanoparticles incorporated biofunctionalized ECM/silk proteins based cardiac patches combined with MSCs for the repair of myocardial infarction: in vitro and in vivo evaluations. Sci Total Environ. 2020;707:135976. doi:10.1016/j.scitotenv.2019.135976

45. Ramirez-Lee MA, Aguirre-Bauelos P, Martinez-Cuevas PP, et al. Evaluation of cardiovascular responses to silver nanoparticles (AgNPs) in spontaneously hypertensive rats. Nanomedicine. 2018;14(2):385395. doi:10.1016/j.nano.2017.11.013

46. Sharma AK, Kumar A, Sahu M, Sharma G, Datusalia AK, Rajput SK. Exercise preconditioning and low dose copper nanoparticles exhibits cardioprotection through targeting GSK-3 phosphorylation in ischemia/reperfusion induced myocardial infarction. Microvasc Res. 2018;120:5966. doi:10.1016/j.mvr.2018.06.003

47. Zhang T, Dang M, Zhang W, Lin X. Gold nanoparticles synthesized from Euphorbia fischeriana root by green route method alleviates the isoprenaline hydrochloride induced myocardial infarction in rats. J Photochem Photobiol B. 2020;202:111705. doi:10.1016/j.jphotobiol.2019.111705

48. Tian A, Yang C, Zhu B, et al. Polyethylene-glycol-coated gold nanoparticles improve cardiac function after myocardial infarction in mice. Can J Physiol Pharmacol. 2018;96(12):13181327. doi:10.1139/cjpp-2018-0227

49. Hosoyama K, Ahumada M, Variola F, et al. Nanoengineered Electroconductive Collagen-Based Cardiac Patch for Infarcted Myocardium Repair. ACS Appl Mater Interfaces. 2018;10(51):4466844677. doi:10.1021/acsami.8b18844

50. You JO, Rafat M, Ye GJ, Auguste DT. Nanoengineering the heart: conductive scaffolds enhance connexin 43 expression. Nano Lett. 2011;11(9):36433648. doi:10.1021/nl201514a

51. Zhang BF, Jiang H, Chen J, Hu Q, Yang S, Liu XP. Silica-coated magnetic nanoparticles labeled endothelial progenitor cells alleviate ischemic myocardial injury and improve long-term cardiac function with magnetic field guidance in rats with myocardial infarction. J Cell Physiol. 2019;234(10):1854418559. doi:10.1002/jcp.28492

52. Gao W, Sun Y, Cai M, et al. Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis. Nat Commun. 2018;9(1):231. doi:10.1038/s41467-017-02657-z

53. Liu N, Chen J, Zhuang J, Zhu P. Fabrication of engineered nanoparticles on biological macromolecular (PEGylated chitosan) composite for bio-active hydrogel system in cardiac repair applications. Int J Biol Macromol. 2018;117:553558. doi:10.1016/j.ijbiomac.2018.04.196

54. Zheng Y, Zhang H, Hu Y, Bai L, Xue J. MnO nanoparticles with potential application in magnetic resonance imaging and drug delivery for myocardial infarction. Int J Nanomedicine. 2018;13:61776188. doi:10.2147/ijn.s176404

55. Xiong YY, Gong ZT, Tang RJ, Yang YJ. The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction. Theranostics. 2021;11(3):10461058. doi:10.7150/thno.53326

56. Huang P, Wang L, Li Q, et al. Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19. Cardiovasc Res. 2020;116(2):353367. doi:10.1093/cvr/cvz139

57. Zhang LL, Xiong YY, Yang YJ. The vital roles of mesenchymal stem cells and the derived extracellular vesicles in promoting angiogenesis after acute myocardial infarction. Stem Cells Dev. 2021;30(11):561577. doi:10.1089/scd.2021.0006

Read the original here:
Therapy and Prevention Strategies for Myocardial Infarction | IJN - Dove Medical Press

Cardiac Stem Cells Comments Off on Therapy and Prevention Strategies for Myocardial Infarction | IJN – Dove Medical Press | October 5th, 2021

Learn how these advanced 3D tissue models generated on the Mantarray platform can improve the physiological relevance of preclinical cardiac and skeletal muscle models, accelerating the discovery of new medicines.

TORONTO (PRWEB) October 05, 2021

3D cellular models and organs-on-chips are poised to add tremendous value by providing human data earlier in the drug discovery pipeline. There is intense interest in adopting these 3D models in preclinical and translational research, but their complex implementation has remained a roadblock for many labs.

In this webinar, Curi Bio will present its Mantarray platform, which represents an easy-to-use, flexible, and scalable system for generating 3D EMTs at high-throughput with the ability to measure contractility in parallel. The platform features a novel method of casting 3D tissues that can be easily performed by nearly any cell biology researcher and can be readily adapted to a variety of cell lines and extracellular matrices. In addition, Mantarrays novel magnetic sensing modality permits contractility measurement of 24 tissues in parallel and in real time, while the cloud data analysis portal takes the guesswork out of analyzing and comparing results across experiments.

Register for this webinar to hear an overview of the technology, along with application examples across various use cases, including:

Learn how these advanced 3D tissue models generated on the Mantarray platform can improve the physiological relevance of preclinical cardiac and skeletal muscle models, accelerating the discovery of new medicines.

Join Dr. Nicholas Geisse, Chief Science Officer at Curi Bio, for the live webinar on Friday, October 22, 2021 at 1pm EDT.

For more information, or to register for this event, visit Mantarray: Scalable Human-Relevant 3D-Engineered Cardiac and Skeletal Muscle Tissues for Safety and Efficacy Studies.

ABOUT XTALKS

Xtalks, powered by Honeycomb Worldwide Inc., is a leading provider of educational webinars to the global life science, food and medical device community. Every year, thousands of industry practitioners (from life science, food and medical device companies, private & academic research institutions, healthcare centers, etc.) turn to Xtalks for access to quality content. Xtalks helps Life Science professionals stay current with industry developments, trends and regulations. Xtalks webinars also provide perspectives on key issues from top industry thought leaders and service providers.

To learn more about Xtalks visit http://xtalks.comFor information about hosting a webinar visit http://xtalks.com/why-host-a-webinar/

Share article on social media or email:

Read the original here:
Mantarray: Scalable Human-relevant 3D Engineered Cardiac and Skeletal Muscle Tissues for Therapeutics Discovery Upcoming Webinar Hosted by Xtalks -...

Cardiac Stem Cells Comments Off on Mantarray: Scalable Human-relevant 3D Engineered Cardiac and Skeletal Muscle Tissues for Therapeutics Discovery Upcoming Webinar Hosted by Xtalks -… | October 5th, 2021

Today is International Heart Day, and Cosmos is looking back on the stories that make our hearts flutter.

Scientists have taken another step in the quest to create a Google map of the human body by putting together a detailed cellular and molecular map of the healthy heart.

An international team analysed almost half a million individual cells and cell nuclei from six different regions of the heart, obtained from 14 organ donors whose hearts were healthy but unsuitable for transplantation.

The result is theHeart Cell Atlas, which, shows the huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells and an intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.

Sometimes, the heart just stops for no perceivable reason. Sudden cardiac arrest (SCA) is a prevalent hidden killer, even for younger people: 40% of those who die from SCA are under 50 years old.

SCA is not as rare as we would like it to be, says cardiologist Elizabeth Paratz, whos undertaking her PhD at the Baker Heart and Diabetes Institute, Melbourne. In the last year in Victoria, 750 young people under 50 have suffered an SCA. This is almost exactly five times the road toll over the same time in this age group, yet we hear a lot more publicity about road fatalities in young people.

Paratz is researching the prevalence and causes of SCA, as well as looking at ways to diagnose it better. There are multiple causes of SCA, and theyre hard to pinpoint in young people.

The controversial use of stem cells to help patients recover from a heart attack may work, but not because it grows new heart muscle.

Research in mice has found that injecting stem cells into the heart triggers an immune response that makes the scar stronger and the heart beat more forcefully.

Thestudy, published in the journalNature, suggests the current practice of injecting stem cells into a patients blood may not be optimal: direct injection into the heart could be more effective.

In a preclinical trial on a beating human heart, researchers have found that a drug candidate developed from the venom of the worlds deadliest spider, the funnel web, may hold promise for heart attack treatment and transplants.

The researchers, led by Meredith Redd of the University of Queensland (UQ), and Sarah Scheuer of Victor Chang Cardiac Research Institute, tested a protein called Hi1a, found in the Fraser Island (Kgari) funnel web venom, on a beating heart that had been exposed to heart attack stresses.

After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle, says Nathan Palpant of UQ, corresponding author of the paper.

The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die.

The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival.

The Chinese Finger Trap a tubular braided novelty beloved by kids and pranksters around the world provided the inspiration for a nifty bit of biotech that looks set to save sick kids a whole lot of heartache. Literally.

Pedro del Nido from Boston Childrens Hospital in the US heads a team that has designed a proof-of-concept device that promises to dramatically cut down on surgery for children with certain types of heart defects.

At present, kids with defective mitral and tricuspid heart valves must undergo surgery in which a corrective implant is installed. The problem, however, is that children grow: the heart increases in size, and requires at least one, and often several, further surgical interventions so that a correspondingly larger implant can be installed.

Needless to say, these repeated bouts of open-heart surgery are extremely traumatic and disruptive.

Now, however, Nido and Karp may have come up with an elegant and clever solution: an implant that grows with the organ.

Link:
Five Heart Stories For International Heart Day - Cosmos

Cardiac Stem Cells Comments Off on Five Heart Stories For International Heart Day – Cosmos | October 5th, 2021

It is too late for conservation efforts to save the northern white rhinoceros, but with recent scientific advancements there may still be hope to bring back this beloved species. In a recently published paper, scientist Marisa Korody and her colleagues at San Diego Zoo Global (USA) and at the Department of Molecular Medicine at Scripps Research (USA) describe their exciting progress on using stem cells to revive the northern white rhino.

The northern white rhino is functionally extinct, meaning there are not enough of these rhinos left to save the species. In fact there are only two northern white rhinos left: a mother and a daughter. But for decades, scientists have preserved cell samples from 15 northern white rhinos containing enough genetic material to potentially bring this species back from the brink. These preserved samples hold fibroblast cells the type of skin cells that secrete collagen from white rhinos. With these scientists newly developed methods, fibroblast cells can be converted into something much more valuable: induced pluripotent stem cells. These stem cells can differentiate into any cell type in the body including heart cells, muscle cells, and reproductive cells.

In theory, by converting fibroblast cells into reproductive cells, scientists could create genetically unique rhino embryos. Alongside other assisted reproduction technologies, scientists could implant a new embryo into a closely-related southern white rhino, where the baby northern white rhino could develop as an otherwise normal pregnancy. By completing this process multiple times, scientists may be able to establish a stable population of northern white rhinos.

In 2011, this research team generated induced pluripotent stem cells from the samples of another endangered species, but unfortunately since this process was found to harm the recipient genomes, this method was largely unsuccessful. Despite this setback, in 2015 the authors met with colleagues worldwide to consider ways to save the northern white rhino, and they concluded that methods involving induced pluripotent stem cells may still be the most promising solution. Over the following years, the scientists worked to improve their methods, and these improvements are documented in their recent paper. These experiments represent the first step in a long-term plan to bring the northern white rhino back through assisted reproduction techniques.

Right from the start, the scientists faced a whole host of challenges. Through trial and error they modified the growth medium for the cells, optimizing it for rhinoceros cells. With their improved growth medium, scientists successfully generated induced pluripotent stem cell lines from 11 rhinoceros individuals. This has never been done before and represents a huge stride forward in the path to recovering this species.

Before trying to make their first rhino, the scientists needed to stress these induced pluripotent stem cells and sequence their genomes to determine if the cell quality is good enough to potentially produce new, viable rhinos. They maintained colonies of these cells in long-term cultures and exposed these colonies to different conditions to give insight into how resilient these cells could be. These tests demonstrated that long-term culture did not affect the potential for these cells to differentiate into cardiac lineage cells, confirming that these cells are stable long-term. The researchers also confirmed that these pluripotent cells could potentially produce gametes, the egg and sperm cells that are used for sexual reproduction. These advancements indicate that with these newly developed protocols, induced pluripotent stem cells are a promising tool that could someday help recover the northern white rhino.

Although this study includes some exciting results, there is still much work to do. For example, scientists must now sequence the genomes of the northern and southern white rhino so other researchers can analyze the stem cells ability to stay the same over time. Despite the work that still needs to be done, these promising advancements could someday help the northern white rhino population recover. This method may also work for saving other endangered or extinct species, as long as the genetic material needed is available. Long-term, these scientists plan to continue a series of experiments that could ultimately bring this beloved rhino, and potentially other endangered species, back from the brink of extinction.

Read more from the original source:
Stem cells may be the key to saving white rhinos from extinction - Sciworthy

Cardiac Stem Cells Comments Off on Stem cells may be the key to saving white rhinos from extinction – Sciworthy | October 5th, 2021

SYDNEY, Oct. 5, 2021 /PRNewswire/ -- Clinical stage drug development company Pharmaxis Ltd (ASX: PXS) today announced further positive results of data analysis from a phase 1c clinical trial (MF-101) studying its drug PXS-5505 in patients with the bone marrow cancer myelofibrosis for 28 days at three dosage levels.

Assessment with Pharmaxis' proprietary assays of the highest dose has shown inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24-hour period at day 7 and day 28. The trial safety committee has reviewed the results and having identified no safety signals, has cleared the study to progress to the phase 2 dose expansion phase where 24 patients will be treated at the highest dose twice a day for 6 months.

Pharmaxis CEO Gary Phillips said, "We are very pleased to have completed the dose escalation phase of this study with such clear and positive findings.We will now immediately progress to the phase 2 dose expansion study where we aim to show PXS-5505 is safe to be taken longer term with the disease modifying effects that we have seen in the pre-clinical models. The trial infrastructure and funding is in place and we are on track to complete the study by the end of 2022."

Independent, peer-reviewed research has demonstrated the upregulation of several lysyl oxidase family members in myelofibrosis.The level of inhibition of LOX achieved in the current study at all three doses significantly exceeds levels that caused disease modifying effects with PXS-5505 in pre-clinical models of myelofibrosis with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. LOXL2 was inhibited to a similar degree and based on pre-clinical work such high inhibition is likely replicated for other LOX family members (LOXL1, 3 and 4).[1] Study data can be viewed in the full announcement.

Commenting on the results of the trial, Dr Gabriela Hobbs, Assistant Professor, Medicine, Harvard Medical School & Clinical Director, Leukaemia, Massachusetts General Hospital said, "Despite improvements in the treatment of myelofibrosis, the only curative therapy remains an allogeneic stem cell transplantation, a therapy that many patients are not eligible for due to its morbidity and mortality. None of the drugs approved to date consistently or meaningfully alter the fibrosis that defines this disease. PXS-5505 has a novel mechanism of action by fully inhibiting all LOX enzymes. An attractive aspect of this drug is that so far in healthy controls and in this phase 1c study in myelofibrosis patients, the drug appears to be very well tolerated. This is meaningful as approved drugs and those that are undergoing study, are associated with abnormal low blood cell counts. Preliminary data thus far, demonstrate that PXS-5505 leads to a dramatic, >90% inhibition of LOX and LOXL2 at one week and 28 days. This confirms what's been shown in healthy controls as well as mouse models, that this drug can inhibit the LOX enzymes in patients. Inhibiting these enzymes is a novel approach to the treatment of myelofibrosis by preventing the deposition of fibrosis and ultimately reversing the fibrosis that characterizes this disease."

The phase 1c/2a trial MF-101 cleared by the FDA under the Investigational New Drug (IND) scheme aims to demonstrate that PXS-5505, the lead asset in Pharmaxis' drug discovery pipeline, is safe and effective as a monotherapy in myelofibrosis patients who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs. Trial sites will now open to recruit myelofibrosis patients into the 6-month phase 2 study in Australia, South Korea, Taiwan and the USA.

An effective pan-LOX inhibitor for myelofibrosis would open a market that is conservatively estimated at US$1 billion per annum.

While Pharmaxis' primary focus is the development of PXS-5505 for myelofibrosis, the drug also has potential in several other cancers including liver and pancreatic cancer where it aims to breakdown the fibrotic tissue in the tumour and enhance the effect of chemotherapy treatment.

Trial Design

Name of trial

PXS5505-MF-101: A phase 1/2a study to evaluate safety, pharmacokinetic and pharmacodynamic dose escalation and expansion study of PXS-5505 in patients with primary, post-polycythaemia vera or post-essential thrombocythemia myelofibrosis

Trial number

NCT04676529

Primary endpoint

To determine the safety of PXS-5505 in patients with myelofibrosis

Secondary endpoints

Blinding status

Open label

Placebo controlled

No

Trial design

Randomised, multicentre, 4 week duration phase 1 (dose escalation) followed by 6 month phase 2 (dose expansion)

Treatment route

Oral

Treatment frequency

Twice daily

Dose level

Dose escalation: three escalating doses

Dose expansion: one dose

Number of subjects

Dose escalation: minimum of three patients to maximum of 18 patients

Dose expansion: 24 patients

Subject selection criteria

Patients with primary or secondary myelofibrosis who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs

Trial locations

Dose escalation: Australia (2 sites) and South Korea (4 sites)

Dose expansion: Australia, Korea, Taiwan, USA

Commercial partners involved

No commercial partner

Reference: (1) doi.org/10.1002/ajh.23409

AUTHORISED FOR RELEASE TO ASX BY:

Pharmaxis Ltd Disclosure Committee. Contact: David McGarvey, Chief Financial Officer and Company Secretary: T +61 2 9454 7203, E david.mcgarvey@pharmaxis.com.au

Join the Pharmaxis mailing listhere

Follow us on LinkedInand Twitter

About Pharmaxis

Pharmaxis Ltd is an Australian clinical stage drug development company developing drugs for inflammatory and fibrotic diseases, with a focus on myelofibrosis. The company has a highly productive drug discovery engine built on its expertise in the chemistry of amine oxidase inhibitors, with drug candidates in clinical trials. Pharmaxis has also developed two respiratory products which are approved and supplied in global markets, generating ongoing revenue.

Pharmaxis is developing its drug PXS-5505 for the bone marrow cancer myelofibrosis which causes a build up of scar tissue that leads to loss of production of red and white blood cells and platelets. The US Food and Drug Administration has granted Orphan Drug Designation to PXS-5055 for the treatment of myelofibrosis and permission under an Investigational Drug Application (IND) to progress a phase 1c/2 clinical trial that began recruitment in Q1 2021. PXS5505 is also being investigated as a potential treatment for other cancers such as liver and pancreatic cancer.

Other drug candidates being developed from Pharmaxis' amine oxidase chemistry platform are targeting fibrotic diseases such as kidney fibrosis, NASH, pulmonary fibrosis and cardiac fibrosis; fibrotic scarring from burns and other trauma; and inflammatory diseases such as Duchenne Muscular Dystrophy.

Pharmaxis has developed two products from its proprietary spray drying technology that are manufactured and exported from its Sydney facility; Bronchitol for cystic fibrosis, which is approved and marketed in the United States, Europe, Russia and Australia; and Aridol for the assessment of asthma, which is approved and marketed in the United States, Europe, Australia and Asia.

Pharmaxis is listed on the Australian Securities Exchange (PXS). Its head office, manufacturing and research facilities are in Sydney, Australia. http://www.pharmaxis.com.au

About PXS-5505

PXS-5505 is an orally taken drug that inhibits the lysyl oxidase family of enzymes, two members LOX and LOXL2 are strongly upregulated in human myelofibrosis. In pre-clinical models of myelofibrosis PXS-5505 reversed the bone marrow fibrosis that drives morbidity and mortality in myelofibrosis and reduced many of the abnormalities associated with this disease. It has already received IND approval and Orphan Drug Designation from the FDA.

Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres.

In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over-stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result.

Myelofibrosis can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of myelofibrosis remains largely unknown. It can be classified as either JAK2 mutation positive (having the JAK2 mutation) or negative (not having the JAK2 mutation).

Source: Australian Leukemia Foundation: https://www.leukaemia.org.au/disease-information/myeloproliferative-disorders/types-of-mpn/primary-myelofibrosis/

Forward-looking statements

Forwardlooking statements in this media release include statements regarding our expectations, beliefs, hopes, goals, intentions, initiatives or strategies, including statements regarding the potential of products and drug candidates. All forward-looking statements included in this media release are based upon information available to us as of the date hereof. Actual results, performance or achievements could be significantly different from those expressed in, or implied by, these forward-looking statements. These forward-looking statements are not guarantees or predictions of future results, levels of performance, and involve known and unknown risks, uncertainties and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this document. For example, despite our efforts there is no certainty that we will be successful in developing or partnering any of the products in our pipeline on commercially acceptable terms, in a timely fashion or at all. Except as required by law we undertake no obligation to update these forward-looking statements as a result of new information, future events or otherwise.

CONTACT:

Media: Felicity Moffatt: T +61 418 677 701, E felicity.moffatt@pharmaxis.com.au

Investor relations:Rudi Michelson (Monsoon Communications) T +61 411 402 737, E rudim@monsoon.com.au

View original content:

SOURCE Pharmaxis Limited

Follow this link:
Pharmaxis Cleared To Progress To Phase 2 Bone Marrow Cancer Trial - WAGM

Cardiac Stem Cells Comments Off on Pharmaxis Cleared To Progress To Phase 2 Bone Marrow Cancer Trial – WAGM | October 5th, 2021

Shahid Akhter, editor, ETHealthworld spoke to Dr. Dinesh Bhurani, Director, Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Centre, to know about the progress of NPRD and the challenges associated with blood stem cell transplants.

How do you think the National Policy for Rare Diseases will impact the treatment of patients suffering from rare blood disorders? Will it help reduce the lag that we often see in policy and practice when it comes to healthcare systems?National Policy on Rare Diseases is a step-in right direction and must be welcomed by the Indian medical fraternity. It not only recognizes rare diseases for the first time in India but also has brought forward the possibility of affordable treatment for life-threatening rare diseases which were not previously covered under the national health program. The policy advocates access for treatment through center of excellences, crowd funding and financial assistance.

The NPRD in a bid to enable patients suffering from rare blood disorders has laid emphasis on the option of one-time curative treatment through hematopoietic stem cell transplant for diseases such as Severe Combined Immunodeficiency (SCID), Chronic Granulomatous disease, Wiskott Aldrich Syndrome, Osteopetrosis, and Fanconi Anaemia. By committing to provide a Rs. 20 lakhs cover for the one-time treatment cost of diseases falling under Group 1 through the umbrella scheme of Rashtriya Arogya Nidhi, the NPRD has attempted to provide coverage to almost 40 per cent of the population who are eligible under the Pradhan Mantri Jan Arogya Yojana. The NPRD as a policy that advocates affordable and accessible healthcare and has the potential to lead to the creation of a conducive healthcare ecosystem whereby multisectoral partnerships can collaboratively work towards reduction in the lag between policy and practice often seen otherwise, thereby leading people to live healthier and fuller lives.

Another reason for low number of donors in India is the misconception that stem cell donation comes with a cost to donor. This idea is completely misplaced and untrue as the cost of procedure starting from sample collection, donation and travel is free of cost, and covered under the cost of treatment of a patient for whom the donation is needed. Added to this is the fact that the number of organizations working in the country in the space of blood stem cell transplant is limited at best, thus awareness generation as compared to other health issues is nominal. However, the situation is gradually evolving and ICMR in its 2021 guidelines has gone on to recognize seven registries across the country as active stakeholders in this ecosystem. This recognition by ICMR will hopefully lead to greater awareness generation.

For blood stem cell transplant knowledge is key in establishing patient donor linkage, and by storing the requisite information with them, these registries do just that. Technology is a tool that has been successfully leveraged by stakeholders in the ecosystem to establish linkages. The Hap- E Search is one such tool that has been used by hospitals in the country to find donor matches for their patients. This software is perhaps one of the most enabling tools available to us in the ecosystem, as it helps find HLA matches not just in the country but across the world. This software is now being used by many government hospitals like AIIMS, Delhi and PGIMER Chandigarh. Once the matching donor is found via the HAP-E Search, the donor is encouraged to make the donation, provided counselling and support to donate blood stem cells, and post donation the stem cells are transported to the patients location.

The NPRD proposed crowdfunding and PPP models to ensure more patients availing treatment for rare diseases. How beneficial do you think such partnerships can be to enable blood stem cell transplant ecosystem?Treatment for rare diseases has been found to be expensive across the world. It is thus that despite stem cell transplants being a proven effective solution in the case of some blood disorders, affordability continues to be a challenge for patients and their families. With treatment costs ranging anywhere between Rs. 15-45 lakh, it remains out of reach for most patients in the country. Also, blood disorders, classified as rare, have limited infrastructure in health systems, networks, and subsidies for patients to access treatments are few. In such a scenario, crowdfunding is definitely a feasible option for patients that would ensure that they do not have to forego treatment due to a paucity of resources.

As per the NPRD, the money raised through crowdfunding would directly get credited to the treatment centre thus ensuring that there is adequate linkage. Further, the public private partnership model suggested by the government has enabled it to avail the support of non- governmental and not-for- profit agencies present in the country. This is truly commendable as not only will this ensure more patient donor linkage in the blood stem transplant ecosystem but will also lead to greater awareness generation and registrations of donors as well. One significant organization that has already partnered with the government in this arena is the DKMS BMST Foundation India. With over 50,000 blood stem cell donors registered with them, this organization has been steadily working towards enabling the ecosystem. In the case of rare diseases, it is imperative that stakeholders do not work in isolation and the government working alongside the private can lead to greater hope for many patients with greater amenities and facilities for treatment being made accessible to them.

Read more from the original source:
Lack of awareness about blood stem cell donation is one of the leading causes for low number of donors in In.. - ETHealthworld.com

Cardiac Stem Cells Comments Off on Lack of awareness about blood stem cell donation is one of the leading causes for low number of donors in In.. – ETHealthworld.com | October 5th, 2021

DBMR has added another report named Exosome therapeutic Market with information Tables for recorded and figure years addressed with Chats and Graphs spread through Pages with straightforward definite examination. The a-list report concentrates on broad assessment of the market development expectations and limitations. The systems range from new item dispatches, extensions, arrangements, joint endeavors, organizations, to acquisitions. This report includes profound information and data on what the markets definition, characterizations, applications, and commitment and furthermore clarifies the drivers and restrictions of the market which is gotten from SWOT investigation. Worldwide market examination report serves a great deal for the business and presents with answer for the hardest business questions. While making Exosome therapeutic Market report, examination and investigation has been completed with one stage or the mix of a few stages relying on the business and customer necessities.

Market definition canvassed in the predominant Exosome therapeutic Market advertising report investigates the market drivers that show factors causing ascend in the market development and market limitations which demonstrate the components causing fall in the market development. It helps clients or other market members to know about the issues they might confront while working in this market throughout a more extended timeframe. This statistical surveying report additionally concentrates on utilization of market, central participants included, deals, value, income and portion of the overall industry with volume and an incentive for every area. The greatness and straightforwardness proceeded in Exosome therapeutic Market business research report makes acquire the trust and dependence of part organizations and clients.

Global Exosome Therapeutic Market By Type (Natural Exosomes, Hybrid Exosomes), Source (Dendritic Cells, Mesenchymal Stem Cells, Blood, Milk, Body Fluids, Saliva, Urine Others), Therapy (Immunotherapy, Gene Therapy, Chemotherapy), Transporting Capacity (Bio Macromolecules, Small Molecules), Application (Oncology, Neurology, Metabolic Disorders, Cardiac Disorders, Blood Disorders, Inflammatory Disorders, Gynecology Disorders, Organ Transplantation, Others), Route of administration (Oral, Parenteral), End User (Hospitals, Diagnostic Centers, Research & Academic Institutes), Geography (North America, Europe, Asia-Pacific and Latin America)

Market Analysis and Insights:Global Exosome Therapeutic Market

Exosome therapeutic market is expected to gain market growth in the forecast period of 2019 to 2026. Data Bridge Market Research analyses that the market is growing with a CAGR of 21.9% in the forecast period of 2019 to 2026 and expected to reach USD 31,691.52 million by 2026 from USD 6,500.00 million in 2018. Increasing prevalence of lyme disease, chronic inflammation, autoimmune disease and other chronic degenerative diseases are the factors for the market growth.

Get Sample Report + All Related Graphs & Charts (with COVID 19 Analysis) @https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-exosome-therapeutic-market&pm

Exosomes are used to transfer RNA, DNA, and proteins to other cells in the body by making alteration in the function of the target cells. Increasing research activities in exosome therapeutic is augmenting the market growth as demand for exosome therapeutic has increased among healthcare professionals.

Increased number of exosome therapeutics as compared to the past few years will accelerate the market growth. Companies are receiving funding for exosome therapeutic research and clinical trials. For instance, In September 2018, EXOCOBIO has raised USD 27 million in its series B funding. The company has raised USD 46 million as series a funding in April 2017. The series B funding will help the company to set up GMP-compliant exosome industrial facilities to enhance production of exosomes to commercialize in cosmetics and pharmaceutical industry.

Increasing demand for anti-aging therapies will also drive the market. Unmet medical needs such as very few therapeutic are approved by the regulatory authority for the treatment in comparison to the demand in global exosome therapeutics market will hamper the market growth market. Availability of various exosome isolation and purification techniques is further creates new opportunities for exosome therapeutics as they will help company in isolation and purification of exosomes from dendritic cells, mesenchymal stem cells, blood, milk, body fluids, saliva, and urine and from others sources. Such policies support exosome therapeutic market growth in the forecast period to 2019-2026.

This exosome therapeutic market report provides details of market share, new developments, and product pipeline analysis, impact of domestic and localised market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, product approvals, strategic decisions, product launches, geographic expansions, and technological innovations in the market. To understand the analysis and the market scenario contact us for anAnalyst Brief, our team will help you create a revenue impact solution to achieve your desired goal.

Grab Your Report at an Impressive 30% Discount! Please click Here @https://www.databridgemarketresearch.com/inquire-before-buying/?dbmr=global-exosome-therapeutic-market&pm

Competitive Landscape and Exosome Therapeutic Market Share Analysis

Global exosome therapeutic market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, company strengths and weaknesses, product launch, product trials pipelines, concept cars, product approvals, patents, product width and breadth, application dominance, technology lifeline curve. The above data points provided are only related to the companys focus related to global exosome therapeutic market.

The major players covered in the report are evox THERAPEUTICS, EXOCOBIO, Exopharm, AEGLE Therapeutics, United Therapeutics Corporation, Codiak BioSciences, Jazz Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, ReNeuron Group plc, Capricor Therapeutics, Avalon Globocare Corp., CREATIVE MEDICAL TECHNOLOGY HOLDINGS INC., Stem Cells Group among other players domestic and global. Exosome therapeutic market share data is available for Global, North America, Europe, Asia-Pacific, and Latin America separately. DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

Many joint ventures and developments are also initiated by the companies worldwide which are also accelerating the global exosome therapeutic market.

For instance,

Partnership, joint ventures and other strategies enhances the company market share with increased coverage and presence. It also provides the benefit for organisation to improve their offering for exosome therapeutics through expanded model range.

Global Exosome Therapeutic Market Scope and Market Size

Global exosome therapeutic market is segmented of the basis of type, source, therapy, transporting capacity, application, route of administration and end user. The growth among segments helps you analyse niche pockets of growth and strategies to approach the market and determine your core application areas and the difference in your target markets.

Based on type, the market is segmented into natural exosomes and hybrid exosomes. Natural exosomes are dominating in the market because natural exosomes are used in various biological and pathological processes as well as natural exosomes has many advantages such as good biocompatibility and reduced clearance rate compare than hybrid exosomes.

Exosome is an extracellular vesicle which is released from cells, particularly from stem cells. Exosome functions as vehicle for particular proteins and genetic information and other cells. Exosome plays a vital role in the rejuvenation and communication of all the cells in our body while not themselves being cells at all. Research has projected that communication between cells is significant in maintenance of healthy cellular terrain. Chronic disease, age, genetic disorders and environmental factors can affect stem cells communication with other cells and can lead to distribution in the healing process. The growth of the global exosome therapeutic market reflects global and country-wide increase in prevalence of autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases, along with increasing demand for anti-aging therapies. Additionally major factors expected to contribute in growth of the global exosome therapeutic market in future are emerging therapeutic value of exosome, availability of various exosome isolation and purification techniques, technological advancements in exosome and rising healthcare infrastructure.

Rising demand of exosome therapeutic across the globe as exosome therapeutic is expected to be one of the most prominent therapies for autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases treatment, according to clinical researches exosomes help to processes regulation within the body during treatment of autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases. This factor has increased the research activities in exosome therapeutic development around the world for exosome therapeutic. Hence, this factor is leading the clinician and researches to shift towards exosome therapeutic. In the current scenario the exosome therapeutic are highly used in treatment of autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases and as anti-aging therapy as it Exosomes has proliferation of fibroblast cells which is significant in maintenance of skin elasticity and strength.

For More Insights Get FREE Detailed TOC @https://www.databridgemarketresearch.com/toc/?dbmr=global-exosome-therapeutic-market&pm

Exosome therapeutic Market Country Level Analysis

The global exosome therapeutic market is analysed and market size information is provided by country by type, source, therapy, transporting capacity, application, route of administration and end user as referenced above.

The countries covered in the exosome therapeutic market report are U.S. and Mexico in North America, Turkey in Europe, South Korea, Australia, Hong Kong in the Asia-Pacific, Argentina, Colombia, Peru, Chile, Ecuador, Venezuela, Panama, Dominican Republic, El Salvador, Paraguay, Costa Rica, Puerto Rico, Nicaragua, Uruguay as part of Latin America.

Country Level Analysis, By Type

North America dominates the exosome therapeutic market as the U.S. is leader in exosome therapeutic manufacturing as well as research activities required for exosome therapeutics. At present time Stem Cells Group holding shares around 60.00%. In addition global exosomes therapeutics manufacturers like EXOCOBIO, evox THERAPEUTICS and others are intensifying their efforts in China. The Europe region is expected to grow with the highest growth rate in the forecast period of 2019 to 2026 because of increasing research activities in exosome therapeutic by population.

The country section of the report also provides individual market impacting factors and changes in regulation in the market domestically that impacts the current and future trends of the market. Data points such as new sales, replacement sales, country demographics, regulatory acts and import-export tariffs are some of the major pointers used to forecast the market scenario for individual countries. Also, presence and availability of global brands and their challenges faced due to large or scarce competition from local and domestic brands, impact of sales channels are considered while providing forecast analysis of the country data.

Huge Investment by Automakers for Exosome Therapeutics and New Technology Penetration

Global exosome therapeutic market also provides you with detailed market analysis for every country growth in pharma industry with exosome therapeutic sales, impact of technological development in exosome therapeutic and changes in regulatory scenarios with their support for the exosome therapeutic market. The data is available for historic period 2010 to 2017.

About Data Bridge Market Research:

An absolute way to forecast what future holds is to comprehend the trend today!Data Bridge set forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process.

Contact:

Data Bridge Market Research

US: +1 888 387 2818

UK: +44 208 089 1725

Hong Kong: +852 8192 7475

Email @ Corporatesales@databridgemarketresearch.com

See the original post here:
Exosome therapeutic Market Report- Trends Key Programs Analysis and Competitive Landscape and Forecast 2028 Amite Tangy Digest - Amite Tangy Digest

Cardiac Stem Cells Comments Off on Exosome therapeutic Market Report- Trends Key Programs Analysis and Competitive Landscape and Forecast 2028 Amite Tangy Digest – Amite Tangy Digest | October 5th, 2021

Trained as a chemist, biophysicist, internist, and cardiologist, Mark Yeager is eager to propel the Frost Institute for Chemistry and Molecular Science into a leading research center.

Even in his youth Mark Yeager could picture the door to his future. Scuffed, chipped, and almost black from layers of varnish, the old, wooden door had a frosted window with five words stenciled in glossy black: Laboratory of Dr. Mark Yeager.

Yet Yeager, the inaugural executive director of the University of Miamis Frost Institute for Chemistry and Molecular Science (FICMS), is quite happy that his new lab in the 94,000-square-foot building slated to open late next year wont even have a door. The $60 million facilitys open floor plan was designed to encourage the free flow of people and ideasand help transform the University into one of the worlds premier research centers for improving the health of humans and that of our planet.

That is the vision, but its not a fantastical vision, said Yeager, a distinguished biophysicist and cardiologist whose top priority is attracting a diverse and elite group of scientists as the institutes first faculty. It is achievable, and it will happen because the University has not wavered in its commitment to elevate STEM (science, technology, engineering, and mathematics) to advance scientific discovery. Theres something going on here thats organic and alive and excitingand Im thrilled to be part of it.

Yeager, whose own groundbreaking research focuses on the molecular causes of heart disease and viral infections, trained as a chemist at Carnegie-Mellon University, as a physician and biophysicist at Yale University and as an internist and cardiologist at Stanford University. He spent two decades at Scripps Research in California, where he established his first independent laboratory, served as the director of research in cardiology, and helped launch the Skaggs Clinical Scholars Program in Translational Research. He has also served as a consultant and scientific and clinical advisor to several biotech companies.

Now he is transitioning to the University from the University of Virginia School of Medicine (UVA), where he chaired the Department of Molecular Biophysics and Biochemistry for nearly a dozen years and helped establish the Sheridan G. Snyder Translational Research Building. At UVA, he also established one of the nations five regional centers for cryo-electron microscopy (cryoEM)the technique he advanced for flash-freezing, imaging, and studying proteins and other macromolecules in their near-natural state.

It is exciting to see the progress being made on the evolution of our Frost Institutes, starting with Data Science and Computing and now the emergence of Chemistry and Molecular Science. We are fortunate to have Mark overseeing our Frost Institute for Chemistry and Molecular Science and working across the entire institutionhis interdisciplinary knowledge and perspective on chemistry are essential for our success, said Jeffrey Duerk, executive vice president for academic affairs and provost. Mark brings a wealth of knowledge and experience to the University of Miami and we are looking forward to his impactful leadership continuing as we move forward.

Yeager said he knew he was making the right career move on his first visit to the University last November. Although the COVID-19 pandemic had curtailed in-person learning and suspended new construction, he heard the unmistakable sound of heavy equipment as he walked past the royal palms and fountain at the end of Memorial Drive, where the five-story FICMS now stands.

I could see an excavation area and heard a cacophony of construction noise where I had a hunch the institute should be, he recalled. That told me that the University was all in. They had made this commitment to fortify STEM and to do transformational science and nothing was going to stop them. In spite of the pandemic, it was all systems go.

The Universitys longtime benefactors, Phillip and Patricia Frost, enabled that commitment in 2017, when they announced their landmark $100 million gift to establish the Frost Institutes for Science and Engineering, now a key initiative of the Roadmap to Our New Centurythe strategic plan guiding the University toward its centennial mark. The umbrella organization for a group of multidisciplinary research centers patterned after the National Institutes of Health and its network of affiliated institutes, the Frost Institutes were envisioned to translate interdisciplinary research into solutions for real-world problems.

Though Yeager officially started his new role on June 1, he has been heavily involved in planning the FICMS' interior for months. He recently placed a $20 million order to equip the facility with five different electron microscopy instruments that chemists, molecular scientists, and engineers will use to explore the molecular structure of exquisitely beam-sensitive soft materials like proteins, hard materials such as metal alloys, as well as nanomaterials comprised of soft and hard components. Along with the buildings state-of-the-art technology and the Universitys research infrastructure, hes confident its location in the heart of the Coral Gables campus will help him recruit a diverse and elite group of scientists who are exploring challenging avenues of impactful researchsomething he has been driven to do almost his entire life.

An occasional songwriter, guitar player, and jogger who in his younger days ran 18 marathons, Yeager was always fascinated by scientific discoveries that illuminated unknown and unseen worlds. A child of the Sputnik era who began entering science fairs in junior high, he began forging his own career as a physician-scientist while in high school in Colorado Springs, Colorado, where his father, an agricultural economist, settled his family after a number of job-related moves.

Inspired by an experiment in Scientific American magazine, he convinced physicians in the therapeutic radiology department at Penrose Hospital to irradiate his fruit flies so he could compare the effects of administering different doses of radiation on their eye pigments. Delivered in Styrofoam cups, his experiments on what is now called dose fractionationand used to reduce tissue damage during cancer treatmentswon him first place in the U.S. Department of Agricultures 1967 International Science Fair and a research stint in an insect toxicology lab in Berkeley, California.

The following summer, when Yeager returned to Penrose Hospital to work as an orderly, he realized that he loved patient care as much as laboratory research and began plotting how he could pursue both careers.

I just got incredible satisfaction from helping patients get out of bed and into a wheelchair, transfer to a gurney, learn to use crutches, recalled Yeager, who joins the University as one of its 100 Talents for 100 Years, a Roadmap initiative to add 100 new endowed chairs to the faculty by the Universitys 2025 centennial. But I also loved chemistry. I loved physics. I loved too many things.

After earning his undergraduate degree in chemistry from Carnegie-Mellon, he was accepted to the Medical Scientist Training Program at Yale University, where, along with his medical degree, he earned his masters degree and doctorate in molecular biophysics and biochemistry. There, he encountered the first of many trailblazing scientists, including two future Nobel laureates, who would influence his lifes work. His Ph.D. advisor, Lubert Stryer, was particularly influential. Stryer authored a premier textbook of biochemistry, pioneered fluorescence-based techniques to explore the motions of biological macromolecules, and made fundamental discoveries on the molecular basis of vision. Yeagers graduate work on rhodopsin, a photoreceptor membrane protein, triggered his fascination with elucidating the molecular bases for such diseases as sudden cardiac death, heart attacks, HIV-1, and other viral infections.

Yeager completed his medical residency and specialized fellowship training in cardiovascular medicine at Stanford University Medical Center, where he managed the pre- and post-operative care of heart transplant patients and wrote 13 chapters in the book Handbook of Difficult Diagnoses.

He also continued exploring cellular biology in the laboratory of Nigel Unwin, who had collaborated with future Nobel laureate Richard Henderson to pioneer the use of cryoEM to determine the molecular structure of membrane proteinsand inspired Yeagers groundbreaking research on gap junction channels. The electrical conduits that connect every cell in the body to its neighbor, gap junction channels play a critical role in maintaining the normal heartbeat.

That research, which Yeager continued at Scripps and at UVA, explained how gap junction channels behave in their normal state, and during an injured state, such as a heart attack. His quest to answer another question particularly relevant todayhow viruses enter host cells, replicate, and assemble infectious particlesis exemplified by his breakthrough research on the assembly, structure, and maturation of HIV-1, the virus that causes AIDS.

Today, those insights, which Yeager humbly calls a few bricks in the edifice of science, hold important clues for developing new, more effective therapies to prevent HIV-1 infection, repair injured tissue, and treat cancer and cardiovascular diseasethe kind of impactful research that the FICMS was designed to advance with collaborative partners across the University, and beyond.

As a pioneer in the field of cryo-transmission electron microscopy, a forefront technology in materials and biological research, Marks expertise and knowledge will position the University as aleader in these cutting-edge fields, said Leonidas Bachas, dean of the College of Arts and Sciences who served as the initial interim director of the FICMS. We look forward to having him lead the Frost Institute for Chemistry and Molecular Science as we continue to advance the sciences, innovate, and expand research collaborations with our faculty and industry partners.

See the rest here:
Distinguished physician-scientist takes the helm of first Frost Institute - University of Miami

Cardiac Stem Cells Comments Off on Distinguished physician-scientist takes the helm of first Frost Institute – University of Miami | October 5th, 2021

A genetic syndrome that affects bones

Osteogenesis Imperfecta (OI) is a hereditary disorder occurring in 1:10,000 births and characterised by osteopenia (bone loss) and skeletal fragility (fractures). Secondary features include short stature, skeletal deformities, blue sclera and dentinogenesis imperfect. (1) There is a large clinical variability in OI, and severity ranges from mild to lethal, based on radiological characteristics. Genetically, OI is a collagen-related syndrome. Type I collagen is a heterotrimeric helical structure synthesized by bone-forming cells (osteoblasts), and it constitutes the most abundant protein of the skeletal organic matrix. (2) Synthesis of type I collagen is a complex process. (3) Collagen molecules are cross-linked into fibrils (which confer tensile strength to the bones). Those are then mineralised by hydroxy-apatites (which provides compressive strength) and assembled into fibres.

Dominant mutations in either the COL1A1 or the COLA1A2 genes are responsible for up to 90% of all OI cases. These mutations (more than 1,000 of which have been identified) lead to impairment of collagen structure and production, which in either quantitative or qualitative bone extracellular matrix (ECM) defects. Mutations affecting ECM structure have serious health consequences because the skeleton protects visceral organs and the central nervous system and provides structural support. Bones also store fat in the yellow bone marrow found within the medullary cavity, whilst the red marrow located at the end of long bones is the site of haematopoiesis. In addition, the ECM constitutes a reservoir of phosphate, calcium, and growth factors, and is involved in trapping dangerous molecules.

Stem cell therapy for OI aims to improve bone quality by harnessing the ability of mesenchymal stem cells (MSC) to differentiate into osteoblasts, with the rationale that donor cells would engraft into bones, produce normal collagen and function as a cell replacement. Stem cells have, therefore, been proposed for the treatment of OI (4) and, in particular, prenatal foetal stem cell therapy (foetal stem cells injected into a foetus, i.e. foetal-to-foetal) approach, which offers a promising route to effective treatment. (5) Human foetal stem cells are more primitive than stem cells isolated from adult tissues and present advantageous characteristics compared to their adult counterparts, i.e. they possess a higher level of plasticity, differentiate more readily into specific lineages, grow faster, senesce later, express higher levels of adhesion molecules, and are smaller in size. (6,7) Prenatal cell therapy capitalises on the small size of the foetus and its immunological naivete. In addition, stem cells delivered in utero benefit from the expansion of endogenous stem cells and may prevent organ injury before irreversible damage. (8)

However, human foetal stem cells used are isolated from either foetal blood drawn by cardiac puncture, either during termination of pregnancy or during ongoing pregnancy, albeit using an invasive procedure associated with a high risk of morbidity and mortality for both the foetus and the mother (9). Foetal cells can also be isolated from the first-trimester liver (following termination of pregnancy) and such cells are currently used in The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial, which aims to investigate the safety and efficacy of transplanting foetal derived MSCs prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI) (10). Alternatively, foetal stem cells can be isolated during ongoing pregnancy from the amniotic fluid, either during mid-trimester amniocentesis or at birth (11,12) or from the chorionic villi of the placenta during first-trimester chorionic villi sampling (13).

We have demonstrated that human fetal stem cells isolated from first trimester blood possess superior osteogenic differentiation potential compared to adult stem cells isolated from bone marrow and to fetal stem cells isolated from first trimester liver. We showed that in utero transplantation of these cells in an experimental model of severe OI resulted in a drastic 75% decrease in fracture rate incidence and skeletal brittleness, and improvement of bone strength and quality.(14) A similar outcome was obtained using placenta-derived foetal stem cells (15) and amniotic fluid stem cells following perinatal transplantation into experimental models. (16,17)

Understanding the mechanisms of action of donor cells will enable the engineering of donor cells with superior efficacy to stimulate bone formation and strengthen the skeleton. Despite their potential to differentiate down the osteogenic lineage, there is little evidence that donor cells contribute to regenerating bones through direct differentiation, due to the very low level of donor cell engraftment reported in all our studies. When placed in an osteogenic microenvironment in vitro, foetal stem cells readily differentiate into osteoblasts and produce wild type collagen molecules. However, there are insufficient proofs that collagen molecules of donor cell origin contribute to the formation of the host bone ECM to confer superior resistance to fracture.

It is now well accepted that stem cells can influence the behaviour of target cells through the release of paracrine factors and, therefore, contribute to tissue regeneration indirectly. We have indeed recently shown that donor stem cells stimulate the differentiation of resident osteoblasts, which were unable to fully mature in the absence of stem cell treatment. (16,17) We are now focusing our efforts on understanding the precise molecular mechanisms by which donor cells improve skeletal health to counteract bone fragility caused by various OI-causative mutations.

References

Please note: This is a commercial profile

2019. This work is licensed under aCC BY 4.0 license.

Editor's Recommended Articles

Read the original here:
Stem cell & gene therapy to treat osteogenesis imperfecta: hype or hope - Open Access Government

Bone Marrow Stem Cells Comments Off on Stem cell & gene therapy to treat osteogenesis imperfecta: hype or hope – Open Access Government | October 5th, 2021