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On the Road As a Stem Cell Courier Press Releases on CSRwire.com – CSRwire.com

By daniellenierenberg

Even in times of the COVID-19 crisis, life-saving blood stem cells are brought to patients - by committed people like Maria

Originally published by DKMS

Maria Schmiing is a DKMS employee and has also been a volunteer stem cell courier for about two years. A few days ago, she took a transplant from Germany to the US - a particularly difficult challenge in times of the COVID-19 crisis. Currently, entry to the US is only possible because DKMS, with the support of the US Stem Cell Donor Register: National Marrow Donor Program (NMDP/Be the Match), has obtained a special permit for stem cell couriers to enter the country - so that patients can receive urgently needed transplants.

"It was through an acquaintance of mine that I became aware of it several years ago. She is a teacher and carries out stem cell transports during the school holidays - I was immediately enthusiastic about it and signed up for it," says Maria Schmiing from Cologne. She applied to Ontime Onboard Courier GmbH, one of the transport companies that DKMS works with to bring life-saving blood stem cells to the recipients.

Maria's first assignment took her to Leiden in the Netherlands - an important place in the fight against blood cancer, as the World Marrow Donor Association (WMDA) has its headquarters there. "I was really excited before I even started the journey," she recalls.

Afterwards many further assignments followed, and it was because of this job as a courier that her desire to work at DKMS was born. "For me, the circle is complete; I'm doing something meaningful with my life. I am very aware of what I am doing this for: for the patients who need our help. What I think is great is that I am also really supported by my team and my managers, especially in the current situation."

Blood stem cell couriers like Maria Schmiing are currently in great demand to ensure that blood stem cell donations reach their recipients all over the world safely, even during the COVID-19 crisis. A few days ago the latest task for the 34-year-old was to travel to the US. "The procedure for a courier mission is actually always the same," she explains, "During the briefing the day before, we go through all documents together and the entire itinerary is discussed. Everything important detail is marked and addressed." But something is different at the moment: the couriers must carry a special permit that allows them to enter the US. "This must be presented upon entry and exit."

The next stop for Maria was the collection centre the next morning. There she received the life-saving blood stem cells from specially trained staff. These had previously been collected from a DKMS donor and prepared for transport. All documents and data were double checked based on the 4 eye principle before the transplant was handed over. "We especially look at the donor number and compare it, because we have to make sure that the patient receives the right transplant".

Afterwards Maria could start her journey. Stem cell couriers are allowed one additional piece of hand luggage only to be able to stay flexible on the way. "Most important are the blood stem cells or the bone marrow. We must not lose sight of the transplant during the entire journey. I look after this suitcase like my own personal treasure, like a mother who looks after her children. I am aware of the responsibility I carry and this stays with me until I have delivered the blood stem cells safely to the patient's clinic."

Before the departure to the US, she made sure that at the Frankfurt Airport the suitcase with the stem cells was not X-rayed. "I always explain that this is harmful to the transplant something most people know. Only after an officer has brought the suitcase through the security area, do I then follow. This is the only time we hand the suitcase over to somebody else. Fortunately, there were no problems either at the security check or at customs.

Once on the plane she informed the crew - an important and regular task for her - and did not let the suitcase out of her sight during the flight. "Sleep, of course, is out of the question. We are not allowed to drink alcohol 24 hours before and during the flight and we of course have to take the suitcase everywhere with us."

Upon arrival in the US, Maria noticed two differences "After landing, several security officers entered the plane and talked to the crew - only then were we allowed to disembark. In addition to this, they took the temperature of all passengers.

She then continued her journey by taxi to the transplant clinic. "Everything went really well, and I was met at the clinic by a member of staff. Again there, we double checked everything and went through the documents according to the four eye principle. Once we get back to Germany, there is also a debriefing and I then return the suitcase."

After handing a transplant over, there is always a moment of great relief for Maria: "The tension disappears. Afterwards she has a ritual, which is very important for her. "I go to the hotel, have a shower and then go out and raise a glass of beer for the patient. I think about how they are doing and what is still ahead of them. I then tell myself that from my side I've done everything I can to help them and I wish them all the best."

Going out and having a beer was not possible this time, as neither shops nor bars were open in the American city - even the hotel restaurant was closed. "I changed my ritual and toasted the unknown patient with a glass of tap water in my room!"

The next day she went back to Germany and soon the next flight will be scheduled for her - couriers are rare in this COVID-19crisis-ridden time. "My learning from this journey: I will take an emergency ration of trail mix with me, you never know," she says with a wink. She reflects on her commitment to patients. "I am still available when my help is needed. I am aware of the risk and take the best possible care and comply with all safety precautions. It is also clear that patients cannot wait - and despite everything with the current situation they should still be given a chance at life.

Learn more about how you can help deleteblood cancer atDKMS.org

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Molecules identified that reverse cellular aging process – New Atlas

By daniellenierenberg

Central to a lot of scientific research into aging are tiny caps on the ends of our chromosomes called telomeres. These protective sequences of DNA grow a little shorter each time a cell divides, but by intervening in this process, researchers hope to one day regulate the process of aging and the ill health effects it can bring. A Harvard team is now offering an exciting pathway forward, discovering a set of small molecules capable of restoring telomere length in mice.

Telomeres can be thought of like the plastic tips on the end of our shoelaces, preventing the fraying of the DNA code of the genome and playing an important part in a healthy aging process. But each time a cell divides, they grow a little shorter. This sequence repeats over and over until the cell can no longer divide and dies.

This process is linked to aging and disease, including a rare genetic disease called dyskeratosis congenita (DC). This is caused by the premature aging of cells and is where the Harvard University team focused its attention, hoping to offer alternatives to the current treatment that involves high-risk bone marrow transplants and which offers limited benefits.

One of the ways dyskeratosis congenita comes about is through genetic mutations that disrupt an enzyme called telomerase, which is key to maintaining the structural integrity of the telomere caps. For this reason, researchers have been working to target telomerase for decades, in hopes of finding ways to slow or even reverse the effects of aging and diseases like dyskeratosis congenita.

Once human telomerase was identified, there were lots of biotech startups, lots of investment, says Boston Childrens Hospital's Suneet Agarwal, senior investigator on the new study. But it didnt pan out. There are no drugs on the market, and companies have come and gone.

Agarwal has been studying the biology of telomerase for the past decade, and back in 2015 he and his team discovered a gene called PARN that plays a role in the action of the telomerase enzyme. This gene normally processes and stabilizes an important component of telomerase called TERC, but when it mutates, it results in less of the enzyme being produced and, in turn, the telomeres becoming shortened prematurely.

For the new study, Harvard researchers screened more than 100,000 known chemicals in search of compounds that could preserve healthy function of PARN. This led them to small handful that seemed capable of doing so by inhibiting an enzyme called PAPD5, which serves to unravel PARN and destabilize TERC.

We thought if we targeted PAPD5, we could protect TERC and restore the proper balance of telomerase, says Harvard Medical Schools Neha Nagpal, first author on the new paper.

These chemicals were tested on stem cells in the lab, made from the cells of patients with dyskeratosis congenita. These compounds boosted TERC levels in those stem cells and restored telomeres to their normal length. However, rather than a scattergun approach, the team really wanted to test for safety and see if the treatment could precisely target stem cells carrying the right ingredients for telomerase formation.

More specifically, the team wanted to see if this could be achieved by having the PAPD5-inhibiting drugs recognize and respond to another important component of telomerase, a molecule called TERT. To do so, in the next round of experiments the team used human blood stem cells and triggered mutations in the PARN gene that give rise to dyskeratosis congenita. These were then implanted into mice that were treated with the compounds, with the team finding the treatment boosted TERC, restored telomere length in the stem cells and had no ill effects on the rodents.

This provided the hope that this could become a clinical treatment, says Nagpal.

The team will now continue its work in an effort to prove these small molecules are a safe and effective way to apply the brakes to dyskeratosis congenita, other diseases, and possibly aging more broadly.

We envision these to be a new class of oral medicines that target stem cells throughout the body, Agarwal says. We expect restoring telomeres in stem cells will increase tissue regenerative capacity in the blood, lungs, and other organs affected in DC and other diseases.

The research was published in the journal Cell Stem Cell.

Source: Boston Childrens Hospital via Harvard University

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Breakthrough to halt premature aging of cells – ScienceBlog.com

By daniellenierenberg

Capping decades of research, a new study may offer a breakthrough in treatingdyskeratosis congenitaand other so-called telomere diseases, in which cells age prematurely.

Using cells donated by patients with the disease, researchers at theDana-Farber/Boston Childrens Cancer and Blood Disorders Centeridentified several small molecules that appear to reverse this cellular aging process.Suneet Agarwal, the studys senior investigator, hopes at least one of these compounds will advance toward clinical trials. Findings werepublished Tuesday in the journal Cell Stem Cell.

If so, it could be the first treatment for dyskeratosis congenita, or DC, that could reverse all of the diseases varying effects on the body. The current treatment, bone marrow transplant, is high-risk, and only helps restore the blood system, whereas DC affects multiple organs.

The compounds identified in the study restore telomeres, protective caps on the tips of our chromosomes that regulate how our cells age. Telomeres consist of repeating sequences of DNA that get shorter each time a cell divides.

The bodys stem cells, which retain their youthful qualities, normally make an enzyme called telomerase that builds telomeres back up again. But when telomeres cant be maintained, tissues age before their time. A spectrum of diseases can result not just DC, but also aplastic anemia, liver cirrhosis, and pulmonary fibrosis.

The discovery of telomerase 35 years ago, earninga Nobel Prize in 2009, galvanized the scientific world. Subsequent studies suggested the enzyme could be a key to reversing aging, as well as treating cancer, in which malignant cells become immortal and divide indefinitely.

For years, researchers have tried to find a simple and safe way to manipulate telomerase, preserve telomeres, and create cures for telomere diseases.

Once human telomerase was identified, there were lots of biotech startups, lots of investment, says Agarwal, who has researched the biology of telomerase for the past decade. But it didnt pan out. There are no drugs on the market, and companies have come and gone.

DC can be caused by mutations in any of multiple genes. Most of these mutations disrupt telomerase formation or function in particular, by disrupting two molecules called TERT and TERC that join together to form telomerase. TERT is an enzyme made in stem cells, and TERC is a so-called non-coding RNA that acts as a template to create telomeres repeating DNA sequences. Both TERT and TERC are affected by a web of other genes that tune telomerases action.

One of these genes is PARN. In 2015, Agarwal and colleagues showed inNatureGeneticsthat PARN is important for processing and stabilizing TERC. Mutations in PARN mean less TERC, less telomerase, and prematurely shortened telomeres.

Thenew study, led by Harvard Medical School postdoctoral fellow Neha Nagpal, delved further, focusing on an enzyme that opposes PARN and destabilizes TERC, called PAPD5.

We thought if we targeted PAPD5, we could protect TERC and restore the proper balance of telomerase, says Nagpal, first author on the paper.

Nagpal and her colleagues first conducted large-scale screening studies to identify PAPD5 inhibitors, testing more than 100,000 known chemicals. They got 480 initial hits, which they ultimately narrowed to a small handful.

They then tested the inhibitors in stem cells made from the Martins cells and those of other patients with DC. To the teams delight, the compounds boosted TERC levels in the cells and restored telomeres to their normal length.

But the real challenge was to see if the treatment would be safe and specific, affecting only the stem cells bearing TERT. To test this, the team introduced DC-causing PARN mutations into human blood stem cells, transplanted those cells into mice, then treated the mice with oral PAPD5 inhibitors. The compounds boosted TERC and restored telomere length in the transplanted stem cells, with no adverse effect on the mice or on the ability to form different kinds of blood cells.

This provided the hope that this could become a clinical treatment, says Nagpal.

In the future, Agarwal, Nagpal, and colleagues hope to validate PAPD5 inhibition for other diseases involving faulty maintenance of telomeres and perhaps even aging itself. They are most excited about two compounds, known as BCH001 and RG7834 that are under further development.

We envision these to be a new class of oral medicines that target stem cells throughout the body, Agarwal says. We expect restoring telomeres in stem cells will increase tissue regenerative capacity in the blood, lungs, and other organs affected in DC and other diseases.

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Autologous Stem Cell Based Therapies Market Demand, Recent Trends and Developments Analysis 2025 – Express Journal

By daniellenierenberg

Latest Market Research Report onAutologous Stem Cell Based Therapies Market size | Industry Segment by Applications (Neurodegenerative Disorders, Autoimmune Diseases? and Cardiovascular Diseases), by Type (Embryonic Stem Cell, Resident Cardiac Stem Cells and Umbilical Cord Blood Stem Cells), Regional Outlook, Market Demand, Latest Trends, Autologous Stem Cell Based Therapies Industry Share & Revenue by Manufacturers, Company Profiles, Growth Forecasts 2025.Analyzes current market size and upcoming 5 years growth of this industry.

TheAutologous Stem Cell Based TherapiesMarketAnalysis report attempts to offer foremost and deep understandings into the current market scenario and the advanced development dynamics. The report onAutologous Stem Cell Based Therapies Marketaims to provides the extensive view of the market landscape. The comprehensive research will enable the well-established as well as the emerging players to expand their business approaches and achieve their targeted goals.

This report on Autologous Stem Cell Based Therapies Market covers the manufacturers data including shipment, revenue, gross profit, business distribution etc., these data help the consumer know about the competitors better. This report also covers topmost regions and countries of the world, which shows a regional development status, including Autologous Stem Cell Based Therapies market size, volume and value as well as price data.

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List of Major Key playersoperating in the Autologous Stem Cell Based Therapies Market are:

The objectives of this report are:

Autologous Stem Cell Based Therapies Market Segmentation by Product Type:

Industry Segmentation by end user:

Most significant topics covered in Autologous Stem Cell Based Therapies market report are:

The foremost points are labelled in detail which are covered in this Autologous Stem Cell Based Therapies Market Report:

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Autologous Stem Cell Based Therapies Market Demand, Recent Trends and Developments Analysis 2025 - Express Journal

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Stem Cell Therapy Market to Discern Steadfast Expansion During 2025 – Cole of Duty

By daniellenierenberg

Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

Know the Growth Opportunities in Emerging Markets

Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

The regional analysis covers:

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Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

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Safety Stem Cells in Spinal Cord Injury – Full Text View …

By daniellenierenberg

This phase I clinical study is an open clinical trial to investigate the safety of the intrathecal application of Neuro-Cells in the treatment of end stage (chronic), traumatic complete (AIS grade A) and incomplete (AIS grade B/C) SCI patients. To that purpose, after inclusion in this study >1 year and less than 5 years after their SCI-event, 10 patients will be included. All patients are invited to visit the trial hospital every month during this 3-months study for appreciation of their possible (S)AEs and/or SUSARs, for physical examination and a biochemical analysis of their blood/urine. Day 0 and day 90 they also undergo a comprehensive neurological examination, the AISIAms, ASIAss and Pain perception.

Finally, the participants are also invited to undergo neurological examinations at day 360 and 720. The purpose of this neurological assessment is to explore in patients if a late administration of Neuro-Cells may have some beneficial effects on the neurological condition of the chronic SCI patient.

All patients undergo a BM harvesting at the start of their participation in the study and will undergo one LP, performed to administer Neuro-Cells. The study is open and descriptive, and no randomization takes place. All patients are followed up until approximately 3 months after the time of administration. After these 3 months, the safety part of this study ends. Patients are invited for a neurological assessment 9 months later (day 360) to explore if Neuro-Cells may have a beneficial effect when given to end stage patients with a traumatic SCI.

The safety part of the study is completed when the last patient finishes his/her visit at day 90. The explorative part of the study ends approximately one year after the time of inclusion at day 720.

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Sustainably Yours: The importance of understanding and trusting in Science – The Phuket News

By daniellenierenberg

In his book 21 Lessons for The 21st Century, historian Yuval Noah Harari begins by writing, In a world deluged by irrelevant information, clarity is power. Before the Internet, access to information was relatively limited, and media was concentrated in the hands of a few corporations, which had its problems.

When it comes to supposed facts about COVID-19 posted on the internet, its best to check first with those doing the real checking: scientists. Photo: AFP

Today, with YouTubers, bloggers, and social media at our fingertips, the world is filled with more information than ever. The problem is that much of it is fake news and rumours. Too many voices are clamouring for our attention, but few are fact-checked for accuracy.

Since the spread of COVID-19 began, weve seen snake oil salesmen hawking cures and prophylaxis, and the spread of conspiracy theories about the viruss origins.

In a world where breathing the same air as someone else can kill you, misinformation can be as deadly as the virus. Now more than ever we need to be mindful of what we say, what we post, and how we behave. So, we need to understand and trust in science.

Why Should We Believe in Science?

According to Harvard Professor Naomi Oreskes, author of Why Trust Science?, for several decades there has been an organised campaign to undermine the publics trust in science funded mainly by industries whose financial interests are threatened by its findings.

At its core, science is the study of how the natural world works.

It has a long history of success, and when done correctly it is the single best method of inquiry we have for the pursuit of truth. Because of science, we have aeroplanes, cars, GPS, the Internet, smartphones and modern medicine. The only reason we know that COVID-19 exists is because of science. More importantly, science is a self-policing system of checks and balances that exists to reveal problems and correct inaccuracies.

It begins with the scientific method, something we all learned in school:

Once a scientist has drawn a conclusion, it undergoes rigorous scrutiny by colleagues who are working in the same discipline. This process of scrutiny can lead to rejecting or accepting the hypothesis, redesigning the experiment or finding additional data to support the conclusion. If the claim is valid, the scientist then publishes their work in a reputable scientific journal such as Nature or Science.

Submission of a paper begins the rigorous peer-review process where experts in the same field deliberately challenge the scientists arguments, inspect their data and look for errors in their methodology. So, before a claim is made and the general media gets a hold of it, a study is peer-reviewed and subjected to scrutiny by dozens, if not hundreds of other experts in the same field.

In areas where there is a scientific consensus, such as the relative safety and efficacy of vaccines, or that climate change is anthropogenic, thousands of studies on these topics have been published over decades and reviewed by thousands of scientists in dozens of countries.

Professor Oreskes notes that a critical aspect of scientific judgment is that it is done collectively and not individually. This weeds out personal biases or someone who might have a specific agenda.

Scientific claims are put through a process much like a trial. Questions are posed, data is analysed, and facts are debated before the community comes to a consensus. This process can take years, even decades. So, when your beliefs are founded on scientific consensus, you are relying on the knowledge of dozens if not hundreds, or thousands of experts in their fields.

Because COVID-19 is still so new, there are lots of unknowns. It will take time to review the data and draw definitive conclusions. There remains speculation about how the virus transmits, whether recovered patients acquire sustained immunity, the effect of heat and humidity have on infection rates and the viability of various treatments, among other things. Nevertheless, our reaction to COVID-19 should be grounded in facts, evidence and empirical data rather than, unfounded opinions, suppositions and fears.

Science Makes Mistakes

Like any other human discipline, science has its failures. For example, in 2014, Japanese biologist Haruko Obokata knowingly falsified data regarding the creation of stimulus acquired pluripotent (STAP) cells in mice. If her claim had been valid, it would have revolutionised the production of embryonic stem cells, which are blank cells that can be programmed to become any of 200 different cell types in the human body, including bone, hair, skin or muscle.

However, due to the self-policing nature of science, within days, other biologists in her field refuted her claims after failing to replicate her experiments. Within months, her paper was retracted, and her career ended in disgrace.

Knowing that science sometimes makes mistakes and admits and corrects for them shouldnt make us trust it any less if anything it should make us believe in it more. Especially when compared to other methods of inquiry, which have no process of scrutiny.

The Problem with Intuition

In his book Thinking Fast Thinking Slow, Nobel Prize-winning behavioural economist Daniel Kahneman defined intuition as, Thinking that you know something without knowing why you do. As an example, he poses this problem:

A bat and ball cost $1.10.

The bat costs one dollar more than the ball.

How much does the ball cost?

If you answered 10 cents, you are incorrect. This question confounds 50% of students from some of the best universities in the world.

The correct answer is 5 cents.

Kahneman identifies two methods for problem-solving. System 1 is quick, intuitive, spontaneous and effortless. It instantly helps us to recognise faces, to act when confronted with dangers and to solve simple questions. System 2 is slow, rational, reflective and effortful. It gets into the drivers seat when you focus and concentrate on a complicated problem.

The problems occur when we try to use System 1 to make complex decisions that require System 2. People will often make judgements based on intuition when a given situation is easy to imagine. For example, when asked what the most dangerous method of generating energy is, public opinion is usually most negative toward nuclear. However, on a per terawatt-hour basis, atomic energy has killed far fewer people than oil, coal and even solar. But because most people conflate nuclear power with war, they tend to answer incorrectly.

When our perception of reality is based on stories that people tell us, rather than science, facts and evidence, it leads to poor decisions. In the modern world, we need to learn to think in terms of data as it is a far too complicated a place to always reason by intuition.

Linear Vs. Exponential Thinking

Part of the reason many governments didnt foresee the problems COVID-19 would create is that their leaders are linear thinkers.

As an example, if you take 30 linear steps, you move 30 standard paces from where you started, or about 30 metres. However, if you take 30 exponential steps, one, two, four, eight, sixteen by the time you get to the last step, you end up a billion metres from where your started thats about 26 times around the planet!

Its the reason why at the beginning of March the United States only had 65 infections and by April 14 it had over 500,000.

We are In This Together

Whether we like it or not, we are in this together. The virus doesnt distinguish between race, social class, tourist, expat or Thai.

We must be careful about what we say or post in social media. The virus kills quickly, but misinformation can also kill by influencing people to do foolish things.

For sources of science that have been peer-reviewed or vetted by experts, you can go to the following websites:

PubMed

The Lancet

Nature Medicine

The New England Journal Of Medicine

The British Medical Journal

WebMD

Healthline

When we depend on intuition, gossip, fake news and conspiracy theories to make decisions, we get leaders who make demonstrably poor decisions that lead to disastrous consequences. In this regard many people think of Donald Trump.

To quote John F. Kennedy, We are not here to curse the darkness, but to light the candle that can guide us through that darkness to a safe and sane future.

Science, both literally and figuratively, is that light; to disregard it is to remain in the dark.

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Stem-Cell Therapy For Cardiac Disease Creative …

By daniellenierenberg

Ischemic heart disease (characterized by decreased blood supply to the heart muscle) is one of the leading causes of death worldwide.It manifests as a coronary artery occlusion, which in turn leads to myocardial infarction, accompanied by death of myocardial cells.This overloads the surviving heart muscle and eventually leads to heart failure.In addition, other causes can also cause heart failure, including chronic hypertension, which is also characterized by the gradual loss of cardiomyocytes, and experimental inhibition of programmed cell death can improve heart function.Clinically, the effective treatment to solve the fundamental problem of heart loss is heart transplantation.The new discovery that stem cells and progenitor cells have regenerative potential to treat and prevent heart failure has changed experimental research and caused explosive growth in clinical research.

Heart RegenerationAlthough heart cells have a slight ability to regenerate.However, it is generally believed that the regenerative capacity of the human heart muscle is seriously insufficient, and it is not enough to make up for the severe loss of myocardium caused by catastrophic myocardial infarction or other heart disease.Studies have found that the heart of some vertebrates (such as zebrafish and salamanders) does undergo a regenerative reaction after injury;under normal conditions, mouse and human cardiomyocytes rarely divide.But after a serious injury, the remaining cardiomyocytes will start DNA synthesis and re-enter the cell cycle.Therefore, the division of existing cardiomyocytes seems to be the most important factor for heart regeneration in mice and humans.The dedifferentiation of cardiomyocytes near the damaged area occurs before their proliferation and is characterized by the loss of expression of myocardial contractile proteins (such as -myosin heavy chain and troponin T). Studies find zebrafish heart regeneration may be mainly caused by undifferentiated stem cells or progenitor cells from the outer layer of the heart (epithelium).Further research on salamanders and zebrafish will more clearly define whether cardiac regeneration in these organisms requires dedifferentiation, proliferation and subsequent cardiomyocyte differentiation, or whether regeneration is driven by the recruitment of stem cells to the injured site.In contrast, in mammalian hearts, cardiomyocytes rarely divide after a myocardial infarction, although transgene overexpression of specific genes in mice increases the division of cardiomyocytes.

There is strong evidence that endothelial cells are renewed by bone marrow-derived progenitor cells, but the idea that cardiomyocytes are renewed by such cells has been heatedly debated. Less controversial is that adult mammalian heart muscle has a resident cardiac stem cell (CSC) population, which has the potential to differentiate into cardiomyocytes and other cell types (such as endothelial and vascular smooth muscle cells). The study found that CSCs can support the basic turnover of cardiomyocytes, but this turnover occurs at a very low rate without damage. CSCs have high proliferation and differentiation potential in vitro, and it may be a promising therapeutic direction to expand autologous CSCs in vitro or stimulate the regeneration of these cells in vivo.

The recognition that there is indeed a regeneration mechanism in the mammalian myocardium has aroused intense attention. Researchers have discovered that it may hinder the existence of aplastic disorders, including ischemia, inflammation and fibrosis at various stages of myocardial infarction. This unfavorable microenvironment may prevent the activation of resident CSCs, thereby reducing the success rate of exogenous cell therapy. Certain components of the inflammatory response may be essential to promote angiogenesis and progenitor cell recruitment, but excessive inflammation may also prevent the recruitment and survival of progenitor cells. Similarly, after myocardial infarction, a certain degree of fibrosis is required to prevent myocardial rupture, but dense fibrosis presents a strong physical barrier to regenerative cells.

Which Stem Cells Are Used In Heart Therapy?Perhaps the most confusing aspect of current cardiac regeneration is the different cell types, which are considered to be candidates for cardiac therapy.Multiple cell candidates reflect that human research on cell regeneration is not deep enough, so further research and exploration are needed.

Figure 1. Many cell types and mechanisms have been proposed for cardiac therapy.

Skeletal MyoblastOne of the earliest cell-based cardiac regeneration strategies was to inject autologous skeletal muscle myoblasts into ischemic myocardium.Myoblasts are resistant to ischemia, and can be differentiated into myotubes (but not into cardiomyocytes) in the laboratory animal experiments and improve ventricular function.The myocardial tube will not integrate with the surviving cardiomyocytes, so it will not beat synchronously with the surrounding myocardium.However, related clinical trials were terminated due to lack of efficacy, so it is unlikely that skeletal myoblasts will actually regenerate the heart muscle.Interestingly, studies found that mouse skeletal muscle contains a large number of non-satellite cells, which can differentiate into spontaneous pulsatile cells with cardiomyocyte characteristics, but no one has found similar cells in human skeletal muscle.

Bone Marrow-Derived Cells

In stem cell cardiac therapy, it was first reported that adult stem cells or progenitor cells transplanted into the infarcted heart of mice that can differentiate into cardiac myocytes are a subset of hematopoietic cells derived from bone marrow. The first evidence that adult bone marrow-derived progenitor cells are involved in the formation of cardiomyocytes in the adult human heart is based on reports of Y chromosome-positive cardiomyocytes in male recipients of transplanted female donor hearts. Animal studies using labeled hematopoietic stem cells for bone marrow transplantation and subsequent myocardial infarction have shown that cardiomyocytes are derived from transplanted cells, but the proportion is extremely low. Moreover, other studies in animals have not demonstrated that hematopoietic progenitor cells can differentiate into cardiomyocytes or improve heart function. Therefore, there is currently no consensus on whether bone marrow-derived progenitor cells differentiate into cardiomyocytes in vivo.

Embryonic stem cell

Embryonic stem (ES) cells are prototype stem cells.They clearly meet all the requirements of stem cells: cloning, self-renewal and multi-potency.ES cells can differentiate into any type of cells present in an adult organism, so it has the potential to completely regenerate the heart muscle.The two obstacles facing the clinical application of ES therapy are immune rejection and the tendency of injecting ES cells to form teratomas.With the increase in knowledge of ES cell differentiation and cardiac embryonic development pathways, ES cell differentiation may become more controllable.Methods to limit teratoma formation include genetic selection of differentiated ES cells, or differentiation of ES cells into cardiomyocytes or endothelial cells in vitro before injection.For example, tumor necrosis factor promotes the differentiation of ES cells into cardiomyocytes.If the differentiated ES cells are delivered to the myocardium in a rich survival mixture, they can survive and improve myocardial function.The inherent difficulty in controlling the growth and differentiation of ES cells and other pluripotent stem cells is that the timing of activating specific signaling pathways may be crucial.For example, recent studies on mouse and zebrafish embryos have shown that the role of the Wnt--catenin pathway in heart development depends on the stage of development.

Endogenous cardiac stem cells

Because allogeneic cells face immunological challenges that may require immune rejection, the isolation of endogenous adult mammalian CSCs based on cell surface markers has attracted great interest. However, no clear CSC mark has been determined so far. Mammalian heart muscle includes a small percentage of stem cells expressing cell surface markers Kitor Scal. In addition, some side population cells also express Kit and / or Sca1, and like Kit +CSC and Sca1 +CSC, side population cells can produce cardiomyocytes in vitro and in vivo. In addition to Kit +CSC, Sca1+CSC and side population cells, the fourth type of CSC also expresses the transcription factor Isl1. The tracer experiments showed that during embryonic heart development, cells expressing Isl1can differentiate into endothelial cells, endocardial cells, smooth muscle cells, conduction system cells, right ventricular myogenic cells and atrial myogenic cells. There are also cells that express Isl1 in the heart of adult mammals, but they are limited to the right atrium, are found in fewer numbers than the embryonic heart, and have unknown physiological effects. Recently, epicardial-derived progenitor cells with angiogenic potential have been described.

Stem cell therapy for heart disease faces some challenges.The most important question to be answered in preclinical research is which stem or progenitor cells are the best choice for treatment.So far, under certain circumstances (acute myocardial infarction), bone marrow-derived progenitor cell therapy has proven to be safe and beneficial, but the regeneration potential of this cell is still controversial.CSC may have the potential to target patients, but isolation and cultivation procedures are still in the early stages of development.ES cells have the greatest differentiation potential, but face moral barriers and the greatest risk of teratoma formation.Whether ES cell derivatives will be rejected by the hosts immune response is still under debate.However, in principle, rejection can be avoided by using cells from a pool of only 150 donors with different HLA types.If new technologies for reprogramming human and mouse fibroblasts into ES-like cells can be used, the use of patient-reprogrammed cells can reduce or even eliminate immune rejection.When designing a more rational cell-based treatment for heart disease, a key issue is to understand the mechanism by which each stem or progenitor cell type can affect myocardial function.Similarly, different cardiology, such as acute myocardial infarction and chronic ischemic cardiomyopathy, may require different types of stem or progenitor cells.

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Reversing diabetes with CRISPR and patient-derived stem cells – FierceBiotech

By daniellenierenberg

Insulin injections cancontrol diabetes, but patients still experience serious complications such as kidney disease and skin infections. Transplanting pancreatic tissues containing functional insulin-producing beta cells is of limited use, because donors are scarce and patients must take immunosuppressant drugs afterward.

Now, scientists atWashington University in St. Louis havedeveloped a way to use gene editing system CRISPR-Cas9 to edit a mutation in human-induced pluripotent stem cells (iPSCs) and then turnthem into beta cells. When transplanted into mice, the cells reversed preexisting diabetes in a lasting way, according to results published in the journal Science Translational Medicine.

While the researchers used cells from patients with Wolfram syndromea rare childhood diabetes caused by mutations in the WFS1 genethey argue that the combination of a gene therapy with stem cells could potentially treat other forms of diabetes as well.

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This virtual event will bring together industry experts to discuss the increasing pace of pharmaceutical innovation, the need to maintain data quality and integrity as new technologies are implemented and understand regulatory challenges to ensure compliance.

One of the biggest challenges we faced was differentiating our patient cells into beta cells. Previous approaches do not allow for this robust differentiation. We use our new differentiation protocol targeting different development and signaling pathways to generate our cells, the studys lead author, Kristina Maxwell, explained in a video statement.

Making pancreatic beta cells from patient-derived stem cells requires precise activation and repression of specific pathways, and atthe right times, to guide the development process. In a recent Nature Biotechnology study, the team described a successful method that leverages the link between a complex known as actin cytoskeleton and the expression of transcription factors that drive pancreatic cell differentiation.

This time, the researchers applied the technology to iPSCs from two patients with Wolfram syndrome. They used CRISPR to correct the mutated WFS1 gene in the cells and differentiated the edited iPSCs into fully functional beta cells.

After transplanting the corrected beta cells into diabetic mice, the animals saw their blood glucose drop quickly, suggesting the disease had been reversed. The effect lasted for the entire six-month observation period, the scientists reported. By comparison, those receiving unedited cells from patients were unable to achieve glycemic control.

RELATED:CRISPR Therapeutics, ViaCyte team up on gene-edited diabetes treatment

The idea of editing stem cells with CRISPR has already attracted interest in the biopharma industry. Back in 2018, CRISPR Therapeutics penned a deal with ViaCyte to develop off-the-shelf, gene-editing stem cell therapies for diabetes. Rather than editing iPSCs from particular patients themselves to correct a faulty gene, the pairs lead project used CRISPR to edit healthy cells so that they lackedthe B2M gene and expressed PD-L1 to protect against immune attack. The two companies unveiled positive preclinical data inSeptember.

Other research groups working on gene therapy or stem cells for diabetes include a Harvard University scientist and his startup Semma Therapeutics, whichdeveloped a method for selecting beta cells out of a mixture of cells developed from PSCs. Scientists at the University of Wisconsin-Madison recently proposed that removing the IRE1-alpha gene in beta cells could prevent immune T cells from attacking them in mice with Type 1 diabetes.

The Washington University team hopes its technology may help Type 1 diabetes patients whose disease is caused by multiple genetic and environmental factors as well as the Type 2 form linked to obesity and insulin resistance.

We can generate a virtually unlimited number of beta cells from patients with diabetes to test and discover new drugs to hopefully stop or even reverse this disease, Jeffrey Millman, the studys co-senior author, said in the video statement. Perhaps most importantly, this technology now allows for the potential use of gene therapy in combination with the patients own cells to treat their own diabetes by transplantation of lab-grown beta cells.

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Repurpose your sleep masks to keep WFH skin fresh and hydrated all day – Well+Good

By daniellenierenberg

Whether youre blasting the heat or AC (or both, because, April), staying inside all day puts you on the fast track to dry skin. Unless youve got a humidifier decorating your WFH space, the air in your home is ripe for sucking the moisture straight out of your face. And while diligently slathering on moisturizer every hour on the hour is certainly one way to hold in the hydration, the easiest method to hydrate skin at home is actually by repurposing your hydrating sleep mask for use during waking hours.

No, were not talking sleeping eye masks. Think of sleep masks, which came to us by way of K-beauty and popularized over the last few years, as a sort of jacket for your skin. Unlike regular masks, they dont need to be washed off, and they create a protective boundary between your skin and environment thats even tougher to permeate than your usual skin products. We recommend using a concentrated mask during the day when working from home, because your skin is so susceptible to losing moisture if you dont adequately hydrate it, says Glow Recipe founder Sarah Lee. Because overnight masks are usually very hydrating with nourishing properties, it really helps to keep that moisture retained throughout the hours. Because of this, its also a great way to maximize the ingredients youre getting from the products youre applying underneath it.

A sleep mask should be the final layer after your usual skin-care routine, and can go on either on top of your moisturizer or in place of it. Scroll through for our favorite picks worth dedicating a spot to in your routine.

This influencer-approved mask is chock full of vitamins (C and E, to be specific) and amino acids that give dull, sleepy skin an instant boost. Its got antioxidants to help protect from free-radical damage, and ceramides to really lock in the moisture it provides.

A combination of watermelon and hyaluronic acid helps to infuse moisture in the skin, and a mixture of AHAs (including glycloic and lactic acids) clear away the top layer of dead skin cells to help moisture penetrate more deeply. The jelly texture is ultra light so that you wont feel like youve got some goopy mask on your face all day long, and can you beat the packaging?

This drugstore beauty buy is not only immensely hydrating (and under $20), but it also leaves behind a pearlescent finish that will make you look luminous while you work. Its formulated with skin-soothing niacinamide and moisture-drawing humectants to hydrate and brighten as it absorbs.

Thanks to its barely-there, water-based formula, this jelly mask absorbs almost immediately into your skin. In addition to highly concentrated mineral water, its also packed with calming and brightening ingredients like orange flower, rose, sandalwood, apricot, and evening primrose. Thirsty pores will drink it right up.

With this mask, youll be waking up, spending your day,and going to sleep beautiful. Its got all kinds of nourishing, natural ingredients like quinoa, mushrooms, and floral stem cells, and is infused with aromatherapy elements to help keep you calm throughout the work day.

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Potential Impact of COVID-19 on Cosmetic Skin Care Market to Show Outstanding Growth by 2025 Profiling Global Players Industry Developments, Outlook,…

By daniellenierenberg

The global Cosmetic Skin Care market reached ~US$ xx Mn in 2019and is anticipated grow at a CAGR of xx% over the forecast period 2019-2029. In this Cosmetic Skin Care market study, the following years are considered to predict the market footprint:

The business intelligence study of the Cosmetic Skin Care market covers the estimation size of the market both in terms of value (Mn/Bn USD) and volume (x units). In a bid to recognize the growth prospects in the Cosmetic Skin Care market, the market study has been geographically fragmented into important regions that are progressing faster than the overall market. Each segment of the Cosmetic Skin Care market has been individually analyzed on the basis of pricing, distribution, and demand prospect for the Global region.

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below:

Global Cosmetic Skin Care Market, Product Analysis

Global Cosmetic Skin Care Market, Application Analysis

In addition the report provides cross-sectional analysis of all the above segments with respect to the following geographical markets:

Global Cosmetic Skin Care Market, by Geography

Each market player encompassed in the Cosmetic Skin Care market study is assessed according to its market share, production footprint, current launches, agreements, ongoing R&D projects, and business tactics. In addition, the Cosmetic Skin Care market study scrutinizes the strengths, weaknesses, opportunities and threats (SWOT) analysis.

COVID-19 Impact on Cosmetic Skin Care Market

Adapting to the recent novel COVID-19 pandemic, the impact of the COVID-19 pandemic on the global Cosmetic Skin Care market is included in the present report. The influence of the novel coronavirus pandemic on the growth of the Cosmetic Skin Care market is analyzed and depicted in the report.

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What insights readers can gather from the Cosmetic Skin Care market report?

The Cosmetic Skin Care market report answers the following queries:

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Breakouts: Why is my skin worse during the coronavirus pandemic? – Express

By daniellenierenberg

The coronavirus crisis is affecting every aspect of our lives, including the condition of our skin. Have you noticed that your skin is particularly spotty, irritated and angry lately? That's another thing you can blame on COVID-19.

Express.co.ukspoke to Dr. Luca Russo, Dermatologist at Urban Retreat, to find out why.Dr. Russo says there are several reasons for your unexpected breakouts.He said: "There might be several reasons for noticing a tendency to break out during this national emergency."It's probably to do with what's going on inside, and what you're putting in your body, says Dr. Russo.

READ MORE- Coronavirus symptoms: Man reveals skin-related warning sign

Are you up all night worrying about the virus?Dr. Russo says: "The most likely cause of your breakout is stress."During such uncertain and stressful times, our system copes with increased production of Cortisol."Cortisol is an androgen hormone that is released when we are facing unusual challenges and prepare us to "fight'."However, it will also increase the sugar level in the bloodstream and production of sebum that might be a cause of the breakout."

In order to prevent breakouts that stem from high levels of stress, you'll need to calm yourself down.Dr Russo recommends doing activities that allow you to relax and unwind, such as yoga.He also suggests exercising regularly, so it's time to start making use of that daily government-approved walk, cycle, or run.

If you hate exercising, don't worry, the antidote to high cortisol levels doesn't have to be physical.Laughing, a solid night of sleep, or practising your favourite hobby are all effective options.

Having a soak in the bath and doing a face-mask may help you feel more in control of your skin.

This relief may cause a decrease in oil production and pimples.

DON'T MISS...How to help your brain through the coronavirus crisis stress [EXPLAINER]Coronavirus: How to look after your mental health during lockdown [EXPLAINER]Lockdown exercise: The eight exercises you can do at home [INFORMER]

Can you honestly say you have been eating well throughout the lockdown?Most people have stocked up on sugary treats and salty snacks in order to cheer themselves up in the face of COVID-19.And what about the good-old "support local businesses" excuse you use every time you order a greasy takeaway?Dr Russo says: "During isolation food becomes one of the few focal points of the day with more consumption of comfort food."Just like any other organ in your body, a poor diet affects your skin negatively.The body breaks down our food into tiny particles of proteins, fats, and carbs, and circulates it to the organs that need them.These nutrients make their way to your skin too, impacting its condition.It makes sense that inflammatory foods, such as sweets, some dairy, processed meat, and refined carbohydrates, will cause a flare-up in your complexion.

Dr. Russo says: "To improve your skin, you must eat well."Eat foods that are packed with vitamins and proteins and snack on fruit and veg."Drinking lots of water will replace the moisture that is lost through sweat and other processes, keeping your skin hydrated.If you fill up on foods rich in healthy oils and omega-3 fatty acids, you will improve the collagen production in your skin.This makes your skin smoother, suppler, and will help you in the longterm by preventing premature ageing.These oils and fats are found in fish, nuts, olive oil, and many more commonly found items.

During the lockdown, we're stuck inside all day and often don't get a chance to let our skin feel the sun.Dr. Russo says: "At the moment, skin isn't being exposed to natural light much at all."When your skin is exposed to natural light, the production of Vitamin D is increased."Endorphins are also produced, and this boosts your immune system and well-being."Make sure you get some fresh air every day, in order to reap these benefits of the sun.The sun is a great natural resource to improve your skin, but make sure you protect yourself with sun protection before you go out.You should wear an SPF of at least 30 on your face whenever you leave the house or are in front of a window for a prolonged amount of time.

Most people are shunning makeup in favour of the natural look since no one other than our household is going to see our faces.This means you may be tempted to skip your cleansing routine and go straight to bed once the day is over.

If you normally get facials and now can't, this may also be why you are breaking out or seeing changes.Dr. Russo explains: "You have probably been unable to receive professional treatments over this time, and this will contribute towards your breakouts."Dr. Russo recommends continuing with your normal skincare routine.He says: "Carry on as normal, but add an exfoliating cleanser to your routine."Exfoliating cleansers make your skincare routine shorter, by combining exfoliating and cleansing in one step.They remove dead skin cells and any build-up of dirt and oil in one go.There are hundreds of physical exfoliating cleansers on the market, as well as chemical exfoliating cleansers, so take your pick!

While surgical masks are thought to protect us against coronavirus, they're not great for our skin, said Dr. Russo.Wearing a mask over your face for many hours is damaging to your skin, especially when it's hot outside.The mask offers the perfect spot for bacteria and germs to harbour.Try double cleansing on the lower half of your face if you've worn a surgical mask for a prolonged period of time.

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Doctors experiment with stem cell therapy on COVID-19 patients – KTVQ Billings News

By daniellenierenberg

Doctors are hoping stem cell therapy could be a weapon in the fight against coronavirus. On Friday, regenerative medicine company Mesoblast announced a 300-person trial to determine whether stem cell treatments will work in COVID-19 patients suffering from severe lung inflammation.

One hospital in New York tried it as an experiment with 12 patients, 10 of whom were able to come off of ventilators.

"What we saw in the very first patient was that within four hours of getting the cells, a lot of her parameters started to get better," Dr. Karen Osman, who led the team at Mount Sinai, told CBS News' Adriana Diaz.

The doctor said she was encouraged by the results, though she was hesitant to link the stem cell procedure to her patients' recovery.

"We don't know" if the 10 people removed from ventilators would not have gotten had they not gotten the stem cells, she said. "And we would never dare to claim that it was related to the cells."

She explained that only a "randomized controlled trial" would be the only way "to make a true comparison."

Luis Naranjo, a 60-year-old COVID-19 survivor, was one of Mount Sinai's stem cell trial success stories. He told Diaz in Spanish that he was feeling "much better."

Naranjo's daughter, Paola, brought him to the emergency room, fearful she would not see her father again. Like so many families struck by the coronavirus, she was not allowed inside with him.

"I forgot to tell him that I love him," she said. "All I said was go inside, I hope you feel better."

During his hospital stay, Naranjo was unconscious and on a ventilator for 14 days.

Doctors proposed giving him stem cells from bone marrow in hopes it would suppress the severe lung inflammation caused by the virus.

Now, Naranjo credits the doctors who treated him for his survival. Though income from his family's jewelry business has been cut off and they found themselves falling behind on rent, Naranjo said he is focused primarily on his recovery and regaining the 25 pounds he lost at the hospital.

Although stem cell treatment, usually reserved for other diseases like rheumatoid arthritis, might end up being another step toward helping coronavirus patients recover, Dr. Osman was quick to say it would not be a "miracle treatment."

"The miracle treatment will be a vaccine," she said.

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BCU biology professor offers tips to prevent COVID-19 infection – Sioux City Journal

By daniellenierenberg

In some patients, COVID-19 has triggered a cytokine storm, an immune system response in which the body attacks its own cells. Jung painted a picture of a boxing match in which "fighter" immune cells are being called upon to battle the virus. This battle generates lots of fluid, waste and pus, making it difficult for the alveoli to pick up the oxygen a person breathes in, leading to multi-organ failure.

"These immune cells, neutrophils and other fighter immune cells, are like that. They don't care if it's a virus or our own cells. If you're infected, they're all enemies," Jung said. "So what they're going to do is they're going to start to kill everybody, basically."

Why exactly some people's immune systems go into overdrive, Jung said, is unknown, but he said it can happen to anybody.

"If we are up to the level where we can fight well without going into a coma or anything, then 14 days later, our body can provide an antibody," Jung said. "An antibody will neutralize this virus very quietly."

Strengthening the immune system

Eating certain foods can help keep your immune cells strong. Jung said vegetables, for example, stimulate the circulation of blood cells from bone marrow.

"Those bioactive reagents can support our immune systems by sending them the appropriate amount of stem cells, just in case some tissue cells are damaged and we need to replenish them. For example, if your lung cell has been damaged and they need to be replaced, that could be done by the stem cell that has been moved from the bone marrow and located around the lung area," said Jung, who encourages eating a variety of different colored vegetables.

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A leader in treating haematological cancers – The Business Times

By daniellenierenberg

Wed, Apr 22, 2020 - 5:50 AM

PATIENTS from around the world have benefited from Parkway Cancer Centre's (PCC) comprehensive and holistic approach to treating haematological cancers, or cancers of the blood. The field of haematology covers a broad spectrum of blood disorders, with the World Health Organization estimating that there are as many as 72 types and sub-types of this form of cancer.

With one of the largest and most experienced teams of haematologists in Singapore - comprising three oncologists and one paediatric oncologist - PCC is able to offer specialised care for the management of a wide range of adult and childhood conditions, including leukaemia and lymphoma, among many others.

Significantly, this core group of haematologists is supported by dedicated transplant physicians, oncology and transplant nurses, transplant coordinators, counsellors and allied health professionals. The breadth of its resources allows PCC to adopt a holistic approach to care that enhances the patient journey and results in better healthcare outcomes.

Treatments provided by the haematology oncology team range from intensive chemotherapy, molecular targeted therapy and novel immunotherapy to stem cell transplantation. For each patient, the team devises a personalised treatment plan that aims to optimise clinical outcomes.

"In all diseases, especially cancers, it is important to be able to see patients as individuals in need of treatment that extends beyond specialised investigations and medications. This is best achieved by a multidisciplinary team approach that identifies the patient's medical and emotional needs, preferences and values," said Dr Colin Phipps Diong, Senior Consultant, Haematology Oncology at PCC.

"We are able to draw on the collective expertise of our multidisciplinary team and use our knowledge bank of experience gleaned from successfully treating some of the most challenging and complex cases. Being at the fore of medical advancements gives us the capability and confidence to provide our patients with current treatment options," he added.

A Pioneer in Bone Marrow Transplantation

Reflecting the depth of its expertise in this specialised field, PCC is the only private healthcare provider that offers a comprehensive adult and paediatric blood and bone marrow transplant programme. Indeed, the centre's haematology team performed the first bone marrow transplant in a private hospital setting in Singapore more than two decades ago.

Bone marrow transplantation, known formally as haematopoietic stem cell transplantation, is a specialised procedure which has proven to be effective in treating many types of cancers, as well as blood and autoimmune disorders such as leukaemia and lymphoma.

Since the 1950s, more than one million transplants have been performed globally, with the success of the procedure largely dependent on the skill and experience of the multidisciplinary transplant team. Transplant specialists at the PCC Haematology and Stem Cell Transplant Centre perform transplants from family members, unrelated donors, and cord blood, for a range of conditions, both non-malignant (thalassaemia, aplastic anaemia) and malignant (acute leukaemias, lymphoma, myeloma).

These specialists have extensive experience in bone marrow transplants in both adult and paediatric patients, having trained and worked at some of the leading transplant centres around the world.

Even though stem cell transplantation has been proven to save lives, there are still risks associated with the procedure. At PCC, these risks are clearly explained to the patients and caregivers before they consent to the procedure. "Complex treatment decisions are regularly discussed between the transplant physicians to formulate an optimal plan for our patients," explained Dr Diong.

The transplantation process involves several important stages: Conditioning where the patient receives chemotherapy and/or radiation to kill the diseased cells and to change the immune system; infusion of healthy stem cells into the body to replace the damaged cells; engraftment, when the transplanted stem cells begin to grow and produce healthy red and white blood cells and platelets over the course of two to four weeks; and post-transplant recovery where the "new" immune system matures and develops the ability to fight infections and blood cancer cells.

Looking ahead, PCC will continue to develop its expertise and services to stay ahead of the curve in treating haematological cancers. "We are always looking ahead. It is important that we build our team further to broaden our regional footprint and expand services to bring our patients access to cutting-edge science like CAR T-cell therapies," said Dr Diong.

"In this regard, we strive to develop services, infrastructure, and facilities that are internationally accredited together with our partners in Parkway. At the same time we will continue to work with all stakeholders to ensure that cost is manageable and more patients have access to our transplant services."

PCC's holistic philosophy

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A rampage through the body – Science Magazine

By daniellenierenberg

The lungs are ground zero, but COVID-19 also tears through organ systems from brain to blood vessels.

Science's COVID-19 coverage is supported by the Pulitzer Center.

The coronavirus wreaked extensive damage (yellow) on the lungs of a 59-year-old man who died at George Washington University Hospital, as seen in a 3D model based on computed tomography scans.

On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure, and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All of the patients shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. They are all COVID positive.

As the number of confirmed cases of COVID-19 approaches 2.5 million globally and deaths surpass 166,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, the virus' reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.

[The disease] can attack almost anything in the body with devastating consequences, says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. Its ferocity is breathtaking and humbling.

Understanding the rampage could help doctors on the front lines treat the roughly 5% of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? And what explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? Taking a systems approach may be beneficial as we start thinking about therapies, says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).

What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body. Despite the more than 1500 papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts like no pathogen humanity has ever seen. Without larger, controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer reviewed. We need to keep a very open mind as this phenomenon goes forward, says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. We are still learning.

WHEN AN INFECTED PERSON expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat. It finds a welcome home in the lining of the nose, according to a recent arXiv preprint, because cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues potentially vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell's machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Or the virus' new victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

If the immune system doesn't beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung's respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.

Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts healthy oxygen transfer. Frontline white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cellspusbehind (see graphic, below). This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration. Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs.

But others deteriorate, often suddenly, developing a condition called acute respiratory distress syndrome. Oxygen levels in their blood plummet, and they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black spaceairshould be. Commonly, these patients end up on ventilators. Many die, and survivors may face long-term complications (see sidebar, p. 359). Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.

Some clinicians suspect the driving force in many gravely ill patients' downhill trajectories is a disastrous overreaction of the immune system known as a cytokine storm, which other viral infections are known to trigger. Cytokines are chemical signaling molecules that guide a healthy immune response; but in a cytokine storm, levels of certain cytokines soar far beyond what's needed, and immune cells start to attack healthy tissues. Blood vessels leak, blood pressure drops, clots form, and catastrophic organ failure can ensue.

Some studies have shown elevated levels of these inflammation-inducing cytokines in the blood of hospitalized COVID-19 patients. The real morbidity and mortality of this disease is probably driven by this out of proportion inflammatory response to the virus, says Jamie Garfield, a pulmonologist who cares for COVID-19 patients at Temple University Hospital.

But others aren't convinced. There seems to have been a quick move to associate COVID-19 with these hyperinflammatory states. I haven't really seen convincing data that that is the case, says Joseph Levitt, a pulmonary critical care physician at the Stanford University School of Medicine.

He's also worried that efforts to dampen a cytokine response could backfire. Several drugs targeting specific cytokines are in clinical trials in COVID-19 patients. But Levitt fears those drugs may suppress the immune response that the body needs to fight off the virus. There's a real risk that we allow more viral replication, Levitt says.

Meanwhile, other scientists are zeroing in on an entirely different organ system that they say is driving some patients' rapid deterioration: the heart and blood vessels.

IN BRESCIA, ITALY, a 53-year-old woman walked into the emergency room of her local hospital with all the classic symptoms of a heart attack, including telltale signs in her electrocardiogram and high levels of a blood marker suggesting damaged cardiac muscles. Further tests showed cardiac swelling and scarring, and a left ventriclenormally the powerhouse chamber of the heartso weak that it could only pump one-third its normal amount of blood. But when doctors injected dye in her coronary arteries, looking for the blockage that signifies a heart attack, they found none. Another test revealed the real cause: COVID-19.

How the virus attacks the heart and blood vessels is a mystery, but dozens of preprints and papers attest that such damage is common. A 25 March paper in JAMA Cardiology found heart damage in nearly 20% of patients out of 416 hospitalized for COVID-19 in Wuhan, China. In another Wuhan study, 44% of 36 patients admitted to the intensive care unit (ICU) had arrhythmias.

The disruption seems to extend to the blood itself. Among 184 COVID-19 patients in a Dutch ICU, 38% had blood that clotted abnormally, and almost one-third already had clots, according to a 10 April paper in Thrombosis Research. Blood clots can break apart and land in the lungs, blocking vital arteriesa condition known as pulmonary embolism, which has reportedly killed COVID-19 patients. Clots from arteries can also lodge in the brain, causing stroke. Many patients have dramatically high levels of D-dimer, a byproduct of blood clots, says Behnood Bikdeli, a cardiovascular medicine fellow at Columbia University Medical Center.

The more we look, the more likely it becomes that blood clots are a major player in the disease severity and mortality from COVID-19, Bikdeli says.

Infection may also lead to blood vessel constriction. Reports are emerging of ischemia in the fingers and toesa reduction in blood flow that can lead to swollen, painful digits and tissue death.

In the lungs, blood vessel constriction might help explain anecdotal reports of a perplexing phenomenon seen in pneumonia caused by COVID-19: Some patients have extremely low blood-oxygen levels and yet are not gasping for breath. In this scenario, oxygen uptake is impeded by constricted blood vessels rather than by clogged alveoli. One theory is that the virus affects the vascular biology and that's why we see these really low oxygen levels, Levitt says.

If COVID-19 targets blood vessels, that could also help explain why patients with pre-existing damage to those vessels, for example from diabetes and high blood pressure, face higher risk of serious disease. Recent Centers for Disease Control and Prevention (CDC) data on hospitalized patients in 14 U.S. states found that about one-third had chronic lung diseasebut nearly as many had diabetes, and fully half had pre-existing high blood pressure.

Mangalmurti says she has been shocked by the fact that we don't have a huge number of asthmatics or patients with other respiratory diseases in her hospital's ICU. It's very striking to us that risk factors seem to be vascular: diabetes, obesity, age, hypertension.

Scientists are struggling to understand exactly what causes the cardiovascular damage. The virus may directly attack the lining of the heart and blood vessels, which, like the nose and alveoli, are rich in ACE2 receptors. By altering the delicate balance of hormones that help regulate blood pressure, the virus might constrict blood vessels going to the lungs. Another possibility is that lack of oxygen, due to the chaos in the lungs, damages blood vessels. Or a cytokine storm could ravage the heart as it does other organs.

We're still at the beginning, Krumholz says. We really don't understand who is vulnerable, why some people are affected so severely, why it comes on so rapidly and why it is so hard [for some] to recover.

THE WORLDWIDE FEARS of ventilator shortages for failing lungs have received plenty of attention. Not so a scramble for another type of equipment: kidney dialysis machines. If these folks are not dying of lung failure, they're dying of renal failure, says neurologist Jennifer Frontera of New York University's Langone Medical Center, which has treated thousands of COVID-19 patients. Her hospital is developing a dialysis protocol with a different kind of machine to support more patients. What she and her colleagues are seeing suggests the virus may target the kidneys, which are abundantly endowed with ACE2 receptors.

According to one preprint, 27% of 85 hospitalized patients in Wuhan had kidney failure. Another preprint reported that 59% of nearly 200 hospitalized COVID-19 patients in China's Hubei and Sichuan provinces had protein in their urine, and 44% had blood; both suggest kidney damage. Those with acute kidney injury were more than five times as likely to die as COVID-19 patients without it, that preprint reported.

The lung is the primary battle zone. But a fraction of the virus possibly attacks the kidney. And as on the real battlefield, if two places are being attacked at the same time, each place gets worse, says co-author Hongbo Jia, a neuroscientist at the Chinese Academy of Sciences's Suzhou Institute of Biomedical Engineering and Technology.

One study identified viral particles in electron micrographs of kidneys from autopsies, suggesting a direct viral attack. But kidney injury may also be collateral damage. Ventilators boost the risk of kidney damage, as do antiviral compounds including remdesivir, which is being deployed experimentally in COVID-19 patients. Cytokine storms can also dramatically reduce blood flow to the kidney, causing often-fatal damage. And pre-existing diseases like diabetes can increase the chances of kidney injury. There is a whole bucket of people who already have some chronic kidney disease who are at higher risk for acute kidney injury, says Suzanne Watnick, chief medical officer at Northwest Kidney Centers.

ANOTHER STRIKING SET of symptoms in COVID-19 patients centers on the brain and nervous system. Frontera says 5% to 10% of coronavirus patients at her hospital have neurological symptoms. But she says that is probably a gross underestimate of the number whose brains are struggling, especially because many are sedated and on ventilators.

Frontera has seen patients with the brain inflammation encephalitis, seizures, and a sympathetic storm, a hyperreaction of the sympathetic nervous system that causes seizurelike symptoms and is most common after a traumatic brain injury. Some people with COVID-19 briefly lose consciousness. Others have strokes. Many report losing their sense of smell and taste. And Frontera and others wonder whether, in some cases, infection depresses the brain stem reflex that senses oxygen starvationanother explanation for anecdotal observations that some patients aren't gasping for air, despite dangerously low blood oxygen levels.

ACE2 receptors are present in the neural cortex and brain stem, says Robert Stevens, an intensive care physician at Johns Hopkins Medicine. And the coronavirus behind the 2003 severe acute respiratory syndrome (SARS) epidemica close cousin of today's culpritwas able to infiltrate neurons and sometimes caused encephalitis. On 3 April, a case study in the International Journal of Infectious Diseases, from a team in Japan, reported traces of new coronavirus in the cerebrospinal fluid of a COVID-19 patient who developed meningitis and encephalitis, suggesting it, too, can penetrate the central nervous system.

But other factors could be damaging the brain. For example, a cytokine storm could cause brain swelling. The blood's exaggerated tendency to clot could trigger strokes. The challenge now is to shift from conjecture to confidence, at a time when staff are focused on saving lives, and even neurologic assessments like inducing the gag reflex or transporting patients for brain scans risk spreading the virus.

Last month, Sherry Chou, a neurologist at the University of Pittsburgh Medical Center, began to organize a worldwide consortium that now includes 50 centers to draw neurological data from care patients already receive. Early goals are simple: Identify the prevalence of neurologic complications in hospitalized patients and document how they fare. Longer term, Chou and her colleagues hope to gather scans and data from lab tests to better understand the virus' impact on the nervous system, including the brain.

No one knows when or how the virus might penetrate the brain. But Chou speculates about a possible invasion route: through the nose, then upward and through the olfactory bulbexplaining reports of a loss of smellwhich connects to the brain. It's a nice sounding theory, she says. We really have to go and prove that.

A 58-year-old woman with COVID-19 developed encephalitis, with tissue damage in the brain (arrows).

Most neurological symptoms are reported from colleague to colleague by word of mouth, Chou adds. I don't think anybody, and certainly not me, can say we're experts.

IN EARLY MARCH, a 71-year-old Michigan woman returned from a Nile River cruise with bloody diarrhea, vomiting, and abdominal pain. Initially doctors suspected she had a common stomach bug, such as Salmonella. But after she developed a cough, doctors took a nasal swab and found her positive for the novel coronavirus. A stool sample positive for viral RNA, as well as signs of colon injury seen in an endoscopy, pointed to a gastrointestinal (GI) infection with the coronavirus, according to a paper posted online in The American Journal of Gastroenterology (AJG).

Her case adds to a growing body of evidence suggesting the new coronavirus, like its cousin SARS, can infect the lining of the lower digestive tract, where ACE2 receptors are abundant. Viral RNA has been found in as many as 53% of sampled patients' stool samples. And in a paper in press at Gastroenterology, a Chinese team reported finding the virus' protein shell in gastric, duodenal, and rectal cells in biopsies from a COVID-19 patient. I think it probably does replicate in the gastrointestinal tract, says Mary Estes, a virologist at Baylor College of Medicine.

Recent reports suggest up to half of patients, averaging about 20% across studies, experience diarrhea, says Brennan Spiegel of Cedars-Sinai Medical Center in Los Angeles, coeditor-in-chief of AJG. GI symptoms aren't on CDC's list of COVID-19 symptoms, which could cause some COVID-19 cases to go undetected, Spiegel and others say. If you mainly have fever and diarrhea, you won't be tested for COVID, says Douglas Corley of Kaiser Permanente, Northern California, co-editor of Gastroenterology.

The presence of virus in the GI tract raises the unsettling possibility that it could be passed on through feces. But it's not yet clear whether stool contains intact, infectious virus, or only RNA and proteins. To date, We have no evidence that fecal transmission is important, says coronavirus expert Stanley Perlman of the University of Iowa. CDC says that, based on experiences with SARS and with the coronavirus that causes Middle East respiratory syndrome, the risk from fecal transmission is probably low.

The intestines are not the end of the disease's march through the body. For example, up to one-third of hospitalized patients develop conjunctivitispink, watery eyesalthough it's not clear that the virus directly invades the eye.

Other reports suggest liver damage: More than half of COVID-19 patients hospitalized in two Chinese centers had elevated levels of enzymes indicating injury to the liver or bile ducts. But several experts told Science that direct viral invasion isn't likely the culprit. They say other events in a failing body, like drugs or an immune system in overdrive, are more likely causes of the liver damage.

This map of the devastation that COVID-19 can inflict on the body is still just a sketch. It will take years of painstaking research to sharpen the picture of its reach, and the cascade of effects in the body's complex and interconnected systems that it might set in motion. As science races ahead, from probing tissues under microscopes to testing drugs on patients, the hope is for treatments more wily than the virus that has stopped the world in its tracks.

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A rampage through the body - Science Magazine

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Researchers use cell therapy to recover damaged brain areas in mice that suffered – Mirage News

By daniellenierenberg

Dispositiu per a realitzar registres electrofisiolgics amb les llums LED incorporades per lus doptogentica.

Equip investigador.

Researchers from Lund University (Sweeden) and the Institute of Neurosciences of the University of Barcelona (UBNeuro) have recovered, through cell therapy, the mobility and sensibility of mice that suffered a cardiovascular accident. The results of this study were published in the journal Proceedings of the National Academy of Sciences (PNAS).

Researchers used an ischemic model of ictus in mice to which they transferred stem cells obtained from the skin of a healthy human donor. The cells were reprogramed to become neuronal progenitors of the damaged area of the brain, specifically the brain cortex. Six months after the transplant, researchers could observe how the new cells had repaired the damage that was caused by the cerebrovascular injury. In addition, the sensor and motor problems resulting from the stroke had been reversed as well.

We observed that the fibers of the cells that were put in the cortical area grew and created connections in brain areas that are far from the transplant area, notes Daniel Tornero, researcher in the Laboratory of Stem Cells and Regenerative Medicine in UBNeuro. To identify the transplanted cells, researches used different techniques that enable the monitoring so as to prove the connection in damaged circuits is right. Although there is a lot of work to do -the researcher adds-, the study sheds light on the possibility of replacing the damaged cells for new healthy cells in patients with ictus.

This is the last study of a series of three articles in which the researchers used cell therapy to work on brain healing. Previous studies showed it is possible to transplant nervous cells derived from human stem cells or reprogrammed cells in the brain of mice affected by cardiovascular injuries. However, researchers did not know whether the transformed cells could create new connections in the mice brains and restore the movement and feelings of touch.

The next step is to understand how the transplant affects intellectual functions such as memory, and the potential adverse effects, concludes Tornero.

Article reference:

S. Palma-Tortosa, D. l Tornero, M. Grnning Hansen, E. Monni, M. Hajy, S. Kartsivadze, S. Aktay, O. Tsupykov, M. Parmar, K. Deisseroth, G. Skibo, O. Lindvall, y Z. Kokaia. Activity in grafted human iPS cellderived corticalneurons integrated in stroke-injured rat brain regulatesmotor behavior. Proceedings of the National Academy of Sciences (PNAS). Doi: doi: 10.1073/pnas.2000690117

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Diabetes Reversed in Mice With CRISPR-Edited Stem Cells From Patients – Technology Networks

By daniellenierenberg

Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes calledWolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

The study is published online April 22 in the journal Science Translational Medicine.

Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.

This is the first time CRISPR has been used to fix a patients diabetes-causing genetic defect and successfully reverse diabetes, said co-senior investigatorJeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

A few years ago, Millman and his colleagues discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, those same researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared quickly in mice with the CRISPR-edited cells implanted beneath the skin, and the animals blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Their newly implanted beta cells could produce insulin, just not enough to reverse their diabetes.

We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation, said co-senior investigatorFumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology. Its a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes in this case, in the Wolfram syndrome gene we can make beta cells that more effectively control blood sugar. Its also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.

In the future, using CRISPR to correct certain mutations in beta cells may help patients whose diabetes is the result of multiple genetic and environmental factors, such as type 1, caused by an autoimmune process that destroys beta cells, and type 2, which is closely linked to obesity and a systemic process called insulin resistance.

Were excited about the fact that we were able to combine these two technologies growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects, Millman said. In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes.

Moving forward, the process of making beta cells from stem cells should get easier, the researchers said. For example, the scientists have developed less intrusive methods, making induced pluripotent stem cells from blood and they are working on developing stem cells from urine samples.

In the future, Urano said, we may be able to take a few milliliters of urine from a patient, make stem cells that we then can grow into beta cells, correct mutations in those cells with CRISPR, transplant them back into the patient, and cure their diabetes in our clinic. Genetic testing in patients with diabetes will guide us to identify genes that should be corrected, which will lead to a personalized regenerative gene therapy.

Reference:

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Induced pluripotent stem cells and CRISPR reversed diabetes in mice – Drug Target Review

By daniellenierenberg

Induced pluripotent stem cells made to produce insulin and CRISPR, used to correct a genetic defect, cured Wolfram syndrome in mice.

Using induced pluripotent stem cells (iPSCs) produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those models.

The findings, from researchers at Washington University School of Medicine in St. Louis, US, suggest this CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

This is the first time CRISPR has been used to fix a patients diabetes-causing genetic defect and successfully reverse diabetes, said co-senior investigator Dr Jeffrey Millman, an assistant professor of medicine and of biomedical engineering at Washington University. For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

Researchers at Washington University School of Medicine in St. Louis have transformed stem cells into insulin-producing cells. They used the CRISPR gene-editing tool to correct a defect that caused a form of diabetes, and implanted the cells into mice to reverse diabetes in the animals. Shown is a microscopic image of insulin-secreting beta cells (insulin is green) that were made from stem cells produced from the skin of a patient with Wolfram syndrome [credit: Millman lab Washington University].

Millman and his colleagues had previously discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, these researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared in mice with the CRISPR-edited cells implanted beneath the skin and the animals blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Although their newly implanted beta cells could produce insulin, it was not enough to reverse their diabetes.

We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation, said co-senior investigator Dr Fumihiko Urano, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology. Its a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes in this case, in the Wolfram syndrome gene we can make beta cells that more effectively control blood sugar. Its also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.

Were excited about the fact that we were able to combine these two technologies growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects, Millman said. In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes.

Moving forward, the process of making beta cells from stem cells should get easier, the researchers said. For example, the scientists have developed less intrusive methods, making iPSCs from blood and they are working on developing stem cells from urine samples.

The study is published in Science Translational Medicine.

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Team Reveal Key to the Survival of Dormant Breast Cancer Cells – Technology Networks

By daniellenierenberg

Most breast cancers utilize the female hormone estrogen to grow, so drug-induced estrogen deprivation is used as a treatment in many patients. However, cancer will recur in one-third of these patients. A research team at Dartmouths and Dartmouth-Hitchcocks Norris Cotton Cancer Center, led by Todd W. Miller, PhD, is trying to understand why dormant breast cancer cells survive despite being starved of estrogen. The team discovered that an anti-diabetes drug, metformin, which is being tested in many clinical trials as an anti-cancer agent, actually activated fat metabolism that protected dormant breast cancer cells during estrogen deprivation. The findings suggest that the drug has context-dependent effects on cancer cells. The results, entitled AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells, are newly published online inClinical Cancer Research, a journal of the American Association for Cancer Research.

Knowledge that metformin has context-dependent effects on cancer cells will inform a better understanding of ongoing and prior clinical trials testing metformin, and help shape the design of trials moving forward. Our study indicates that the development of drugs targeting fat metabolism is warranted for breast cancer. Most excitingly, anti-angina drugs that block fat metabolism may be quickly repurposed as potential treatments for cancer and tested in clinical trials, says Miller.

Next steps include clinical trials testing drugs that block fat metabolism in breast cancer. Were also designing preclinical studies to further dissect the roles of fat metabolism in breast and other cancers, with the goal of identifying more refined therapeutic targets that will selectively kill cancer cells and not harm healthy cells, notes Miller.

Reference:Hampsch, et al. (2020) AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells. Clinical Cancer Research DOI: 10.1158/1078-0432.CCR-20-0269.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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