Jagasia was concerned that although G.V.H.D. was the most likely diagnosis, it might not be the right one. The patient had already been tested for the usual infections seen in immune-suppressed patients. So he looked for other possible causes of the patients diarrhea. He didnt find any. The patient lost another 15 pounds. When he looked in the mirror, he hardly recognized himself. Jagasia arranged for the patient to start getting intravenous nutrition and began tapering one immune-suppressing medication in order to start another.

The patients son was in medical school in another part of the state and called home frequently. When his father finally told him how sick he was, his son got scared. His father was a minimizer. If he was saying this, things must be bad.

When he got off the phone, the young man immediately turned to the internet. He typed in gastroenteritis after ... stem-cell transplant. The first results that came up referred to a paper in a medical journal, Clinical Infectious Diseases, published nearly a decade earlier that identified an unexpected culprit: norovirus.

Norovirus is one of the most common causes of gastroenteritis in the world. In the United States, its linked to an estimated 21 million cases of nausea and vomiting every year. Diarrhea can be present but is not typically as severe as other symptoms. In a normal host, the infection resolves on its own after 48 to 72 hours, thanks to the hard work of the immune system. Even so, norovirus was not a common cause of diarrhea in those who are immunosuppressed. But in the medical-journal paper, the first of its kind, 12 patients who had a stem-cell transplant and developed a persistent diarrheal illness were found to have norovirus. And of those 12, 11 were initially thought to have G.V.H.D. In most of those cases, it was only after the immune-suppressing medications were reduced that the patients own defenses could come to the rescue and vanquish the virus.

The son immediately sent the paper to his father. Had he been tested for norovirus? he asked. The patient wasnt sure. He forwarded the journal article to Jagasia and asked if hed had this test. He hadnt. Jagasia was 99 percent certain that this was a wild-goose chase. Hed never seen norovirus in patients with compromised immune systems. Still, testing was easy.

When the test came back positive, Jagasia was stunned. He repeated the test. Positive again. He immediately started to taper the immune-suppressing medications. As the doses came down, the diarrhea slowed, and after a few weeks, it stopped completely. With the help of the IV nutrition, and a slowly improving appetite, the patient began to gain back the weight he lost. From the patients point of view, his son saved his life.

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His Immune System Went Out of Whack. The Usual Treatment Didnt Work. Why? - The New York Times

Skin Stem Cells Comments Off on His Immune System Went Out of Whack. The Usual Treatment Didnt Work. Why? – The New York Times | March 18th, 2020

A research team led by Professor Michael Sieweke, from the Center for Regenerative Therapies TU Dresden (CRTD) and the Center of Immunology of Marseille Luminy (CNRS, INSERM, Aix-Marseille University), has uncovered a surprising property of blood stem cells that contributes to boosting our immunity.

Not only do the stem cells ensure the continuous renewal of blood cells and contribute to the immune response triggered by an infection, but they can also remember previous infectious encounters to drive a more rapid and more efficient immune response in the future.

These cells are found within the soft tissue, or bone marrow, in the centre of large bones such as the hip and thigh bones.

The new findings should have a significant impact on future vaccination strategies and pave the way for new treatments of an underperforming or over-reacting immune system.

Stem cells in our bodies act as reservoirs of cells that divide to produce new stem cells, as well as a myriad of different types of specialised cells that are required to secure tissue renewal and function.

Commonly called blood stem cells, the hematopoietic stem cells (HSC) are found in the bone marrow, the soft tissue that is in the centre of large bones such as the hips or thighs. The role of the cells is to renew the repertoire of blood cells, including cells of the immune system, which are crucial to fight infections and other diseases.

Work from Professor Michael Siewekes laboratory and others over the past years has proven the dogma that HSCs were unspecialised cells, blind to external signals such as infections, was wrong, and has shown that HSCs can actually sense external factors to specifically produce subtypes of immune cells on demand to fight an infection.

Beyond their role in an emergency immune response, the question remained as to the function of HSCs in responding to repeated infectious episodes. The immune system is known to have a memory that allows it to better respond to returning infectious agents. The present study now establishes a central role for blood stem cells in this memory.

Professor Michael Sieweke, Humboldt Professor at TU Dresden, CNRS Research Director and last author of the publication, explained how they found the memory was stored within the cells: The first exposure to LPS causes marks to be deposited on the DNA of the stem cells, right around genes that are important for an immune response. Much like bookmarks, the marks on the DNA ensure that these genes are easily found, accessible and activated for a rapid response if a second infection by a similar agent was to come.

The authors further explored how the memory was inscribed on the DNA, and found C/EBPb to be the major actor, describing a new function for this factor, which is also important for emergency immune responses. Together, these findings should lead to improvements in tuning the immune system or better vaccination strategies.

Sieweke concluded: The ability of the immune system to keep track of previous infections and respond more efficiently the second time they are encountered is the founding principle of vaccines.

Now that we understand how blood stem cells bookmark immune response circuits, we should be able to optimise immunisation strategies to broaden the protection to infectious agents. It could also more generally lead to new ways to boost the immune response when it underperforms or turn it off when it overreacts.

The results of this research are published in Cell Stem Cellon March 12, 2020.

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Stem cells: what do bones have to do with boosting immunity? - Health Europa

Bone Marrow Stem Cells Comments Off on Stem cells: what do bones have to do with boosting immunity? – Health Europa | March 17th, 2020

A BUCKLEY man is one step closer to a clean bill of health after receiving life-saving treatment.

The Leader previously reported that Matt Davies was given 12-months to live without a stem cell transplant, which sparked a massive support network, with thousands signing up to become a donor.

Wife Sarah Davies urged people to sign up to become a donor, which could save the lives of many people and over 7,000 had signed up from her link alone.

Before Christmas, Matt was given the news that there was a match for him and he could start his treatment in January.

She told the Leader: It was a success, at the moment the cells in his body are 99.5 per cent donor and 0.5 per cent his. In time they will be 100 per cent donor so its definitely working which is fantastic.

We are on day 67 and on day 100 we can have a bone marrow scan to find out what stage we are.

GvHD is our biggest worry at the moment. Small amounts after a transplant can be good because it means his body is fighting but in huge amounts it can be damaging. It is starting to affect his gut now.

Because we live in Wales and have done for several years, we couldnt get the funding for the therapy which is what the Christie does, but we are now in the process of getting the drug for him, we are in constant talks so its a frustrating game at the moment.

We need to start this medication to get rid of this GvHD before it becomes chronic, so we are still in the process of getting that drug but hes doing really well.

Graft versus host disease (GvHD) is a condition that might occur after a transplant. In GvHD, the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells then attack the body.

Matt was diagnosed with cancer last year and beat it, however less than eight months later after having his three-monthly routine bone marrow results he was told the leukaemia was back and his only option was a stem cell transplant.

He has since made significant progress however the pair say they are worried about the latest coronavirus outbreak due to Matt essentially having no immune system.

Sarah said: At the moment with coronavirus its very scary because he has a low immune system, he is basically starting from scratch with his immune system so cant get immunisations until he is one year old. We have decided to take the kids out of school because we dont want him catching anything.

Hes done absolutely fantastic and is now back to eating.

Matt has been really lucky. They are pleased with his progress, but they would like his GvHD levels to be lower.

Although Matt faced no real complications during the treatment however has lost a significant amount of weight.

A JustGiving Page has been set up to raise funds for the Christie in Manchester where Matt has been receiving his treatment.

Sarah added: Even still now I will be walking somewhere and random people who Ive never met before will ask me how he is doing. Its actually been so positive. I dont think people realise how much it has helped, just them asking it has really helped us get through this and knowing that a lot of people are supporting us.

On social media we have spoken to so many people in similar situations as ours, its about helping one another, and we have made friends for life.

Thank you so much for your support, it means a lot to us and its lovely for us to read all the comments, even if we cannot reply to them all.

Matts progress can be found on social media via the Team Davies Facebook and Instagram page.

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Buckley couple thank community for their support as dad-of-two receives life-saving treatment | The Leader - LeaderLive

Bone Marrow Stem Cells Comments Off on Buckley couple thank community for their support as dad-of-two receives life-saving treatment | The Leader – LeaderLive | March 17th, 2020

Today, we will see why Fate Therapeutics (FATE) is an attractive pick in March 2020.

Fate Therapeutics is a clinical-stage biopharmaceutical company focused on the development of next-generation cellular immunotherapies for cancer and immune disorders. The company has pioneered proprietary iPSC (induced pluripotent stem cell) platform technology to develop off-the-shelf cell-based cancer immunotherapy products. Current patient-derived autologous and allogeneic cell therapies suffer from drawbacks such as high costs, manufacturing complexity, product heterogeneity, and high turnaround time. These methods, including patient and donor-derived approaches to cell therapy, also require batch-to-batch sourcing and engineering of millions of primary cells.

Fate Therapeutics aims to be the game-changer in cell-based cancer immunotherapy space by enabling the development of off-the-shelf cell products derived from master cell lines. The company aims to develop less costly, homogenous, and multi-dose or multi-cycle cell therapies with small turnaround time. The resultant cell therapy products are expected to be well-defined and uniform in the composition and can be mass-produced at a significant scale in a cost-effective manner and can be delivered off-the-shelf for broad patient accessibility.

The company's cell therapy pipeline comprises immune-oncology programs including off-the-shelf NK- and T-cell product candidates derived from master iPSC lines, and immuno-regulatory programs, including product candidates to prevent life-threatening complications in patients undergoing hematopoietic cell transplantation and to promote immune tolerance in patients with autoimmune disease.

Human-induced Pluripotent Stem cells are generated by reprogramming adult somatic cells to a pluripotent state. Fibroblasts are the most commonly used primary somatic cell type for the generation of induced pluripotent stem cells. They are reprogrammed using retroviruses. Pluripotent cells are capable of differentiating in all cell types that make up the body.

A single human iPSC can potentially differentiate into more than 200 cell types and provides a renewable source for making cells.

NK (natural killer) cells are the body's first line of defense against tumors and various pathogens. Fate Therapeutics is leveraging its iPSC platform to produce off-the-shelf NK cell therapy products.

FT500 is Fate Therapeutics' first off-the-shelf iPSC-derived NK-cell product candidate. The FT500 study is an open-label, multi-dose Phase 1 clinical trial designed to evaluate FT500 for the treatment of advanced solid tumors.

The dose-escalation stage of the study was originally designed to assess the safety and tolerability of three once-weekly doses of FT500, without IL-2 cytokine support, as a monotherapy and in combination with one of three FDA-approved ICI (immune checkpoint inhibitor) therapies in patients that have failed prior ICI therapy.

Data for the first 12 patients in the Phase 1 study has demonstrated clean safety for the iPSC platform. The cutoff date considered was November 28, 2019. It was seen that there were no reported dose-limiting toxicities, no FT500 related Grade 3 or greater adverse events or serious adverse events, and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease.

Further, the trial also involved the evaluation of a multi-dose treatment course consisting of outpatient lympho-conditioning followed by three once-weekly doses of FT500 over up to two 30-day treatment cycles. Here, based on patients' T-cell and antibody repertoire, no anti-product immune responses against FT500 were evident over the multi-dose treatment course.

A total of 62 doses of FT500 were administered to these 12 patients in a safe and well-tolerated manner. Initial clinical data thus provides strong evidence that multiple doses of iPSC-derived NK-cells can be delivered off-the-shelf without patient matching.

In December 2019, the company disclosed plans to amend the trial protocol by including IL-2 cytokine support with each dose of FT500 after completion of 300 million cells per dose cohort in the ICI combination arm. The company has commenced dose-expansion part of Phase 1 trial with 300 million cells per dose and is focusing on enrolling NSCLC patients who are refractory to or have relapsed following CBT. This tumor type is highly susceptible to NK-cell recognition and killing. The study is enrolling at three clinical sites in the U.S. Fate Therapeutics expects expansion data readout from the trial in the second half of 2020.

Fate Therapeutics is studying the second product candidate from iPSC product platform and off-the-shelf NK-cell cancer immunotherapy, FT516, in an open-label, multi-dose Phase 1 trial. This product has been engineered to augment antibody-dependent cellular cytotoxicity.

In December 2019, the company announced results for two patients dosed with FT516. FT516 was administered as a monotherapy to the first patient who was suffering from relapsed/refractory AML (acute myeloid leukemia). The company dosed FT516 in combination with rituximab to the second patient who was suffering from high-risk DLBCL (diffuse large B-cell lymphoma) and had relapsed after multiple rituximab combination regimens, autologous hematopoietic stem cell transplant, and CAR (chimeric antigen receptor) T-cell therapy. The patients had received a first treatment cycle consisting of outpatient lympho-conditioning, three once-weekly doses of FT516 and IL-2 to better promote NK-cell activity.

Initial clinical data based on bone marrow biopsy at day 42 demonstrated no morphologic evidence of leukemia. There was even evidence of hematopoietic recovery following the completion of the first FT516 treatment cycle in the AML patient. There was also no circulating leukemia cells in the patient's peripheral blood. The patient even reported the recovery of neutrophils without growth factor support. The data did not demonstrate dose-limiting toxicities, although serious adverse events were seen. Initial dose escalation data may be read out in the second half of 2020.

This initial clinical evidence highlights the high probability of engineered iPSC-derived NK-cells demonstrating anti-tumor activity in AML indication. Besides, there is a body of data that has demonstrated clinical proof-of-concept for donor-derived NK-cell therapy in relapsed refractory AML and relapsed refractory DLBCL.

In December 2019, FDA accepted FT516's second IND application for studying the product in combination with PDL1, PD1, EGFR and HER2-targeting monoclonal antibody therapies in solid tumor indications. Initially, the company plans to prioritize the combination of FT516 and avelumab in patients with advanced solid tumors who are refractory to or have relapsed following, at least one line of anti-PDL1 monoclonal antibody therapy. The company plans to initiate enrollment in a clinical trial for FT516 and avelumab in mid-2020.

Fate Therapeutics is studying off-the-shelf multi-antigen targeted CAR NK-cell product candidate, FT596, in solid tumor indications.

In December 2019, Fate Therapeutics reported favorable in vivo preclinical data for FT596.

Here, in humanized mouse models of lymphoma and leukemia, FT596's efficacy was comparable to that of primary CAR T-cells in promoting tumor clearance and extending survival. FT596 combined with rituximab also showed the enhanced killing of lymphoma cells in vivo as compared to rituximab alone. FT596 can thus emerge to be best-in-class off-the-shelf treatment in B-cell malignancies. Fate Therapeutics has started enrolling patients in the open-label Phase I study. Initial dose escalation data readout on FT596 is expected in the second half of 2020.

Fate Therapeutics has high hopes for FT596, considering that initial clinical data from a donor-derived CAR19 NK-cell program at MD Anderson, demonstrated a 73% overall response rate in patients with relapsed refractory non-Hodgkin's lymphoma and chronic lymphocytic leukemia with no major toxicities. Hence, while the efficacy seemed similar to CAR T therapy, the safety profile was differentiated in favor of CAR NK-cell therapies.

Although early, this data has highlighted CAR NK-cells' capacity to confer a high level of efficacy without the CAR-T cell therapy-related toxicities. Fate Therapeutics expects FT596 to effectively replace patient-specific and allogeneic CAR19 T-cell immunotherapies. The latter single-antigen specific and hence pose a risk of disease relapse due to antigen escape as well as cause significant toxicities due to off-target activity. FT596, on the other hand, has been engineered with three active anti-tumoral functional components.

Fate Therapeutics aims to be the first company to introduce off-the-shelf iPSC-derived CAR T-cell therapy to patients, FT819, by submitting IND in the second quarter of 2020. The company expects to file an IND application for off-the-shelf CRISPR-edited, iPSC-derived NK-cell product candidate, FT538, by early May 2020. The company has also planned IND submission for FT576 in the second half of 2020.

Although Fate Therapeutics is pioneering a revolutionary approach for mass production of off-shelf cell therapy products, its pipeline is very early stage. There has not been sufficient data from its clinical programs to make an informed estimate about the success probability of these programs. In this backdrop, the company is exposed to significant R&D failure risks. In case data readouts from FT500 and FT596 clinical programs do not match expectations, the company may witness increased share price volatility.

At the end of 2019, the company had cash worth $261 million on its balance sheet. The company spent cash worth $83.2 million on operating activities in 2019. This is a proxy for the 2019 cash burn rate. We assume that the annual cash burn rate in 2020 will be around $120 million, considering that three assets have entered in-human trials. Hence, the company seems to have cash that can sustain operations until the end of 2021. However, if cash is needed at a faster pace, the company may land up requiring more funds. This can lead to equity dilution.

According to finviz, the 12-month consensus target price of Fate Therapeutics is $37.94. On March 4, Citi analyst Yigal Nochomovitz reiterated the "Buy" rating and increased target price from $26 to $41. On March 4, Barclays analyst Peter Lawson also initiated coverage of Fate Therapeutics with an Overweight rating and $40 price target.

On March 3, BMO Capital analyst Do Kim raised the firm's price target on Fate Therapeutics to $28 from $22 and reiterated the "Market Perform" rating. On March 3, Guggenheim analyst Michael Schmidt reiterated the "Buy" rating and increased target price from $25 to $41. On March 3, Roth Capital analyst Tony Butler reiterated the "Neutral" rating but increased the target price from $20 to $30. On March 3, BTIG analyst Amanda Murphy reiterated the "Buy" rating and increased target price from $27 to $42. The analyst has also raised the estimated value of the company's iPSC platform from $740 million to $2.0 billion.

On March 3, Oppenheimer analyst Matthew Biegler reiterated the "Outperform" rating and increased the target price from $27 to $36. Piper Sandler analyst, Edward Tenthoff also reiterated the "Overweight" rating and raised the target price from $28 to $57.

In September 2019, Fate Therapeutics launched in-house GMP (Good Manufacturing Practices) manufacturing facility at headquarters in San Diego, California. This is custom designed to use clonal master iPSC lines as a renewable cell source for the consistent and scaled manufacture of off-the-shelf NK-cell and CAR T-cell products. The company has already produced hundreds of cryopreserved, infusion-ready doses of FT500, FT516, and FT596 at a low cost per dose. Currently stored in inventory, these doses are immediately available for use in the clinical settings.

The full control of cGMP production and the technical expertise to genetically engineer iPSCs and create qualified clonal master lines for clinical use implies that the company has operational expertise and redundancies required for the consistent cost-effective manufacturing and clinical supply of off-the-shelf cell products.

I believe that the 12-month target price of $30 fairly reflects the growth potential as well as risks associated with early-stage Fate Therapeutics. I consider this company to be a good pick for aggressive biotech investors with an investment horizon of at least one year.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Fate Therapeutics: Potential Catalysts Ahead - Seeking Alpha

Bone Marrow Stem Cells Comments Off on Fate Therapeutics: Potential Catalysts Ahead – Seeking Alpha | March 17th, 2020

After the World Health Organization (WHO) declared that thecoronavirus outbreakis officially a pandemic, countries around the world have responded accordingly.Universitiesin Canada and the US are closing, non-essential conferences andsports leaguesare being canceled, and people are being advised to halt all travel plans. Anyone can get infected, and the only way to slow down the outbreak is toreduce the number of people getting infected.

Amidst this fear, the most widespread advice for anyone experiencing symptoms is tosocially distance themselves. But what, exactly, does that mean? How is this different from self-isolation? What if you live with family? What if only one person in a family of four is experiencing symptoms? Why is this even important?

How do I know if I need to socially distance myself? How is that different from self-isolation and strict isolation?

Everyone should besocially distancingthemselves! Essentially, that means deliberately distancing yourself from other individuals to reduce COVID-19 transmission rates.

On the other hand,self-isolationor self-quarantine is when you have been in contact with someone who was diagnosed with the coronavirus, or someone who was exhibiting symptoms. Self-isolation also applies for people who are asymptomatic, but have secondary medical issues (diabetes, heart condition) that may make a coronavirus infection more dangerous for them.

Lastly,isolationis when you have been diagnosed with COVID-19, or if you are exhibiting any flu-like symptoms. At this point, you will receive instructions for isolation from your medical provider.

What does social distancing entail?

If possible,do not leave the house. Try to stay at least six feet away from other people, and avoid coming in direct contact with them. Social distancing can also be done by avoiding crowds and mass gatherings, canceling upcoming events, working from home, moving classes online, and communicating electronically instead of personally visiting people.

What if I live with other people?

Even if no one in the household is exhibiting symptoms, it is best to keep distance for at least two weeks, which would be the viruss incubation period.On the other hand, if you need to self-isolate, try to sleep in separate rooms, and keep6 feet away from each other. Frequently wash your hands, andfrequently keep your surrounding areas clean. If possible, avoid touching your face, especially after being in contact with shared possessions or furniture. Wash all plates and utensils thoroughly with warm soap and water, or use a dishwasher with a drying cycle.

How can I help vulnerable people?

If there are vulnerable and at-risk individuals in your neighborhood, consider getting groceries and other essentials for them, and leave the items at their doorstep. Frequently call or check up on your friends and family, since social distancing can be quite lonely.

Why is social distancing important for everyone, including young and asymptomatic people?

According to data fromSouth Korean authorities, translated byDr. Eric Feigl-Ding, young people between the ages of 20 and 29 are carrying 30% of the disease in South Korea, with the majority beingasymptomatic, meaning they are not experiencing symptoms. This means that while you mayfeelfine, if you are sick you can still infect a large number of people by just being out and about!

Why is social distancing important?

By now you have probably seen a version of the graph that explains why we need to "flatten the curve." Through social distancing and pro-active measures, we can not only delay the "peak" of the outbreak, easing demand for hospital and emergency services, but can also reduce how bad the outbreak could be.

Do you still have questions about social distancing, isolation, or anything else about the coronavirus pandemic?

Ask our community of scientists now!

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What does social distancing really mean? - Massive Science

Skin Stem Cells Comments Off on What does social distancing really mean? – Massive Science | March 17th, 2020

For their study, Terzic and colleagues analyzed the hearts of mice that received cardiopoietic stem cell therapy as well as those that did not. They used an algorithmic approach to map the proteins in the heart muscle, identifying 4,000 proteins. Ten percent of these were damaged during a heart attack.

The investigators found that the therapy either fully or partially reversed two-thirds of the changes caused by the event. And about 85% of cellular functional categories impacted by infarction responded positively to treatment, the authors wrote. They also noted that new blood vessels and heart tissue began to grow as a result of the intervention.

In the United States, someone has a heart attack every 40 seconds, according to the study, which kills this precious cardiac tissue and leads to a significantly weaker heart. Although cardiopoietic stem cells are still being investigated in advanced clinical trials in human patients, this most recent study is a big step in the right direction.

The current findings will enrich the base of knowledge pertinent to stem cell therapies and may have the potential to guide therapeutic regimens in the future," Terzic concluded.

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Stem cell therapy revives cardiac muscle damaged during heart attacks - Cardiovascular Business

Bone Marrow Stem Cells Comments Off on Stem cell therapy revives cardiac muscle damaged during heart attacks – Cardiovascular Business | March 17th, 2020

The northern white rhino population is in jeopardy

The northern white rhino is one of the animal kingdoms many majestic giants, but years of poaching has taken a toll on their population. From 1970 to 1980, their numbers plummeted from 500 to 15 as illegal hunters pursued white rhinos for the ivory of their horns.

Things started to turn around during the 1990s and 2000s, groups and individuals began to crack down on poachers within the white rhinos range. As a result, the population of white rhinos in the wild recovered slightly, peaking at around 32 individuals.

Since 2003, the rate of white rhino poaching has been on the rise and has affected the animals numbers. As of 2008, northern white rhinos have been declared extinct in the wild, and in 2018, the last male northern white rhino died. Now, there are only two of these magnificent beasts left on Earth. Both of them are females.

Najin and Fatu are the last two northern white rhinos in existence. They live at the Ol Pejeta Conservancy in Kenya, and they could be the species last hope for the future. In 2014, keepers in the Czech Republic collected sperm samples from a male northern white rhino living in their care.

Those samples were frozen and stored, and later, they were used in an attempt to breed Najin and Fatu. Both attempts at inducing pregnancies in the two female rhinos were unsuccessful, forcing scientists to consider new methods of approach for saving the white rhinos from extinction.

Typically, when a species is placed on the endangered list, a recovery plan is established by whatever local conservancy group oversees the population. From there, breeding programs of captive individuals are used to begin bolstering the number of individuals on the planet.

When healthy breeding populations have been established, in most cases, reintroduction begins. Small populations of the species are released into the wild to begin repopulation. However, in the case of the northern white rhinos, scientists and conservationists alike have been stuck at step two for decades.

Unwillingness and inability to breed arent uncommon among captive species and individuals, and in most cases, zoos can jockey animals around until a pair matches and produces offspring. In the case of Najin and Fatu, the options for procreation are far more limited. Even the fallback of artificial insemination isnt working for them, so what are scientists to do?

Weve revived entire species from the dead before, but it has never been an easy task. Fortunately, the world of reproductive sciences has been evolving quickly, and conservationists and animal experts now have myriad options to choose from when it comes to creating new life.

Neither surviving female is healthy enough to birth live young. Aside from that, there is the added challenge of finding an option that preserves the northern white rhino genome while maintaining high enough levels of viability.

One possible route to repopulation involves approaching conventional methods from a new and enlightened angle. Although neither Najin nor Fatu can bear young, they both still produce viable egg cells, which can be harvested, frozen, and kept in a lab.

Much like humans undergoing fertility therapy or other conception aids, the grandmother-granddaughter pair or northern white rhinos can hope for success through in-vitro fertilization. This method of conception combines sperm and multiple egg cells in an external environment before implanting them in a host mother.

By using multiple eggs during the in-vitro process, the chances for success, even in females with fertility issues, is significantly increased. In some fortunate cases, the method is so effective, and it results in multiple pregnancies. Once the sperm has fertilized the eggs, the cells are transferred to a living host.

While Najin and Fatu may not be the physical mothers of any of their calves, modern reproductive science has made it possible for their genes to be passed on to another generation.

How? with modern science, a surrogate mother from the thriving population of southern white rhinos could become the mother to their children.The two types of animals have similar enough reproductive organs and their eggs could be used in place of Najin or Fatus.

While the animals are compatible, gathering eggs from them is a far more complicated procedure.

Researchers working on bringing back the northern white rhinos have managed to gather a few eggs so far, but not nearly enough to repopulate an entire species.

Its no secret that rhinoceroses are large animals. Just as cattle and horses have significantly larger hearts than we humans do, rhinos have much larger reproductive organs. Locating and withdrawing eggs from a rhinos ovaries is a far greater ordeal than it is for humans.

To complicate matters further, the ovaries of a southern white rhino are located three to four feet from her rump, and the veterinarian seeking to collect the eggs must guide a probe that distance up her rectum and into an ovary before using a catheter to remove the eggs.

The procedure is anything but easy. In addition to the difficulty involved in the process of extracting eggs, the success rate of current methods is hardly ideal. Researchers working on bringing back the northern white rhinos have managed to gather a few eggs so far, but not nearly enough to repopulate an entire species.

The odds of reestablishing a sustainable population of northern white rhinos through in-vitro fertilization and surrogacy currently seem pretty slim. Fortunately for the rhinos, science has a few other methods up its sleeve.

In the last decade, stem cell research has gone from a thing of whimsy to an advanced field of study that continues to improve by leaps and bounds with every passing year. Its applications are seemingly endless, and they just might be the answer that the northern white rhino conservationists have been looking for.

Stem cells are sort of like biological canvases. They come in different varieties: Totipotent, pluripotent, multipotent, oligopotent, and unipotent. Each of these types has unique limitations and can be found in various sources from embryonic tissue to adult bone marrow.

To make baby rhinos, scientists have been focused on induced pluripotent stem cells, which are gathered and grown from the skin of adult white rhinos

A cell from your bicep and a cell from your gametes (sperm or egg) both hold the same blueprints; they just come in different packaging.

Pluripotent cells behave similarly to embryonic stem cells, which can be coaxed into becoming just about any other type of cell. In this case, even though the original cells were taken from the skin of adult rhinos, they can be trained to become something different, such as egg cells.

Using what knowledge we currently have of stem cells and their manipulation, scientists can tell a northern white rhinos skin cell to become a viable egg or sperm cell. From there, they can attempt in-vitro fertilization and implantation into a surrogate, even without fertile parents.

The method is still in its infancy, but it has been successfully carried out more than once.

With stem cells as a backup and surrogates abound, Najin and Fatu have plenty of options. In late 2019, conservationists and rhinos alike received promising news. Eggs gathered from the two northern white rhinos had been fertilized and resulted in successful embryos. Those embryos were frozen in liquid nitrogen and prepared for a long journey.

Waiting down in southern Africa are the lucky mamas who will become the surrogates for the next generation of northern white rhinos. The embryos have quite a ways to travel before they can be implanted. After that, they can grow within their new mother for the 16 to 18-month gestation period typical of white rhinos.

Although the methods of creating viable embryos are currently long, challenging, and not terribly efficient, these babies-to-be are incredibly promising first steps. In addition to the two successful in-vitro attempts in September, December of 2019 saw the creation of a third viable embryo.

2020 will undoubtedly see further attempts at creating more embryos. With luck, we can soon hope to hear news of successful implantations in surrogate moms. In 2021, we can throw a worldwide baby shower for some bouncing baby northern white rhinos, whose births will serve as a beacon of hope for a dying species.

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Can hybrid embryos save the white rhinos from extinction? - Science 101

Bone Marrow Stem Cells Comments Off on Can hybrid embryos save the white rhinos from extinction? – Science 101 | March 17th, 2020

Newswise What gets the leader of the NIH jazzed?

Speaking to a packed West Pavilion auditorium March 6, Francis Collins, M.D., Ph.D., director of the National Institutes of Health, shared his picks of 10 areas of particular excitement and promise in biomedical research. (Watch the full talk here.)

In nearly every area, UAB scientists are helping to lead the way as Collins himself noted in several cases. At the conclusion of his talk, Collins addedhis advice for young scientists. Here is Collins top 10 list, annotated with some of the UAB work ongoing in each area and ways that faculty, staff and students can get involved.

1. Single-cell sequencing

[see this section of the talk here]

I am so jazzed with what has become possible with the ability to study single cells and see what they are doing, Collins said. They have been out of our reach now we have reached in. Whether you are studying rheumatoid arthritis, diabetes or the brain, you have the chance to ask each cell what it is doing.

Single-cell sequencing and UAB:Collins noted that Robert Carter, M.D., the acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was a longtime faculty member at UAB (serving as director of the Division of Clinical Immunology and Rheumatology). For the past several years, UAB researchers have been studying gene expression in subpopulations of immune cells inpatients with rheumatoid arthritis.

Join in:Researchers can take advantage of the single-cell sequencing core facility in UABsComprehensive Flow Cytometry Core, directed by John Mountz, M.D., Ph.D., Goodwin-Blackburn Research Chair in Immunology and professor in the Department of Medicine Division of Clinical Immunology and Rheumatology.

Learn more:Mountz and other heavy users of single-cell sequencing explain how the techniqueslet them travel back in time and morein this UAB Reporter story.

2. New ways to see the brain

[See this section of the talk here]

The NIHsBRAIN Initiativeis making this the era where we are going to figure out how the brain works all 86 billion neurons between your ears, Collins said. The linchpin of this advance will be the development of tools to identify new brain cell types and circuits that will improve diagnosis, treatment and prevention of autism, schizophrenia, Parkinsons and other neurological conditions, he said.

Brain tech and UAB:Collins highlighted thework of BRAIN Initiative granteeHarrison Walker, M.D., an associate professor in the Department of Neurology, whose lab has been developing a more sophisticated way to understand the benefits of deep brain stimulation for people with Parkinsons and maybe other conditions, Collins said.

Join in:UABs planned new doctoral program in neuroengineering would be the first of its kind in the country.

Learn more:Find out why neuroengineering is asmart career choicein this UAB Reporter story.

3. Induced pluripotent stem (iPS) cells

[See this section of the talk here]

Researchers can now take a blood cell or skin cell and, by adding four magic genes, Collins explained, induce the cells to become stem cells. These induced pluripotent stem (iPS) cells can then in turn be differentiated into any number of different cell types, including nerve cells, heart muscle cells or pancreatic beta cells. The NIH has invested in technology to put iPS-derived cells on specialized tissue chips. Youve got you on a chip, Collins explained. Some of us dream of a day where this might be the best way to figure out whether a drug intervention is going to work for you or youre going to be one of those people that has a bad consequence.

iPS cells at UAB:Collins displayed images of thecutting-edge cardiac tissue chipdeveloped by a UAB team led by Palaniappan Sethu, Ph.D., an associate professor in the Department of Biomedical Engineering and the Division of Cardiovascular Disease. The work allows the development of cardiomyocytes that can be used to study heart failure and other conditions, Collins said.

Join in:UABs biomedical engineering department, one of the leading recipients of NIH funding nationally, is a joint department of the School of Engineering and School of Medicine. Learn more about UABsundergraduate and graduate programs in biomedical engineering, and potential careers, here.

Learn more:See howthis novel bioprinterdeveloped by UAB biomedical researchers is speeding up tissue engineering in this story from UAB News.

4. Microbiome advances

[See this section of the talk here]

We have kind of ignored the fact that we have all these microbes living on us and in us until fairly recently, Collins said. But now it is clear that we are not an organism we are a superorganism formed with the trillions of microbes present in and on our bodies, he said. This microbiome plays a significant role not just in skin and intestinal diseases but much more broadly.

Microbiome at UAB:Collins explained that work led by Casey Morrow, Ph.D., and Casey Weaver, M.D., co-directors of theMicrobiome/Gnotobiotics Shared Facility, has revealed intriguing information abouthow antibiotics affect the gut microbiome. Their approach has potential implications for understanding, preserving and improving health, Collins said.

Join in:Several ongoing clinical trials at UAB are studying the microbiome, including a studymodifying diet to improve gut microbiotaand an investigation of the microbiomes ofpostmenopausal women looking for outcomes and response to estrogen therapy.

Learn more:This UAB News storyexplains the UAB researchthat Collins highlighted.

5. Influenza vaccines

[See this section of the talk here]

Another deadly influenza outbreak is likely in the future, Collins said. What we need is not an influenza vaccine that you have to redesign every year, but something that would actually block influenza viruses, he said. Is that even possible? It just might be.

Influenza research at UAB:Were probably at least a decade away from a universal influenza vaccine. But work ongoing at UAB in the NIH-fundedAntiviral Drug Discovery and Development Center(AD3C), led by Distinguished Professor Richard Whitley, M.D., is focused on such an influenza breakthrough.

Join in:For now, the most important thing you can do to stop the flu is to get a flu vaccination. Employees can schedule afree flu vaccination here.

Learn more:Why get the flu shot? What is it like? How can you disinfect your home after the flu? Get all the information atthis comprehensive sitefrom UAB News.

6. Addiction prevention and treatment of pain

[See this section of the talk here]

The NIH has a role to play in tackling the crisis of opioid addiction and deaths, Collins said. The NIHs Helping to End Addiction Long-term (HEAL) initiative is an all-hands-on-deck effort, he said, involving almost every NIH institute and center, with the goal of uncovering new targets for preventing addiction and improving pain treatment by developing non-addictive pain medicines.

Addiction prevention at UAB:A big part of this initiative involves education to help professionals and the public understand what to do, Collins said. The NIH Centers of Excellence in Pain Education (CoEPE), including one at UAB, are hubs for the development, evaluation and distribution of pain-management curriculum resources to enhance pain education for health care professionals.

Join in:Find out how to tell if you or a loved one has a substance or alcohol use problem, connect with classes and resources or schedule an individualized assessment and treatment through theUAB Medicine Addiction Recovery Program.

Learn more:Discover some of the many ways that UAB faculty and staff aremaking an impact on the opioid crisisin this story from UAB News.

7. Cancer Immunotherapy

[See this section of the talk here]

We are all pretty darn jazzed about whats happened in the past few years in terms of developing a new modality for treating cancer we had surgery, we had radiation, we had chemotherapy, but now weve got immunotherapy, Collins said.

Educating immune system cells to go after cancer in therapies such as CAR-T cell therapy is the hottest science in cancer, he said. I would argue this is a really exciting moment where the oncologists and the immunologists together are doing amazing things.

Immunotherapy at UAB:I had to say something about immunology since Im at UAB given that Max Cooper, whojust got the Lasker Awardfor [his] B and T cell discoveries, was here, Collins said. This is a place I would hope where lots of interesting ideas are going to continue to emerge.

Join in:The ONeal Comprehensive Cancer Center at UAB is participating in a number of clinical trials of immunotherapies.Search the latest trials at the Cancer Centerhere.

Learn more:Luciano Costa, M.D., Ph.D., medical director of clinical trials at the ONeal Cancer Center, discusses the promise ofCAR-T cell therapy in this UAB MedCast podcast.

Assistant Professor Ben Larimer, Ph.D., is pursuing a new kind of PET imaging test that could give clinicians afast, accurate picture of whether immunotherapy is workingfor a patient in this UAB Reporter article.

8. Tapping the potential of precision medicine

[See this section of the talk here]

The All of Us Research Program from NIH aims to enroll a million Americans to move away from the one-size-fits-all approach to medicine and really understand individual differences, Collins said. The program, which launched in 2018 and is already one-third of the way to its enrollment goal, has a prevention rather than a disease treatment approach; it is collecting information on environmental exposures, health practices, diet, exercise and more, in addition to genetics, from those participants.

All of Us at UAB:UAB has been doing a fantastic job of enrolling participants, Collins noted. In fact, the Southern Network of the All of Us Research Program, led by UAB, has consistently been at the top in terms of nationwide enrollment, as School of Medicine Dean Selwyn Vickers, M.D., noted in introducing Collins.

Join in:Sign up forAll of Usat UAB today.

Learn more:UABs success in enrolling participants has led to anew pilot study aimed at increasing participant retention rates.

9. Rare diseases

[See this section of the talk here]

Rare Disease Day, on Feb. 29, brought together hundreds of rare disease research advocates at the NIH, Collins said. NIH needs to play a special role because many diseases are so rare that pharmaceutical companies will not focus on them, he said. We need to find answers that are scalable, so you dont have to come up with a strategy for all 6,500 rare diseases.

Rare diseases at UAB: The Undiagnosed Diseases Network, which includes aUAB siteled by Chief Genomics Officer Bruce Korf, M.D., Ph.D., is a national network that brings together experts in a wide range of conditions to help patients, Collins said.

Participants in theAlabama Genomic Health Initiative, also led by Korf, donate a small blood sample that is tested for the presence of specific genetic variants. Individuals with indications of genetic disease receive whole-genome sequencing. Collins noted that lessons from the AGHI helped guide development of the All of Us Research Program.

Collins also credited UABs Tim Townes, Ph.D., professor emeritus in the Department of Biochemistry and Molecular Genetics, for developing the most significantly accurate model of sickle cell disease in a mouse which has been a great service to the [research] community. UAB is now participating in anexciting clinical trial of a gene-editing technique to treat sickle cellalong with other new targeted therapies for the devastating blood disease.

Join in:In addition to UABs Undiagnosed Diseases Program (which requires a physician referral) and the AGHI, patients and providers can contact theUAB Precision Medicine Institute, led by Director Matt Might, Ph.D. The institute develops precisely targeted treatments based on a patients unique genetic makeup.

Learn more:Discover how UAB experts solved medical puzzles for patients by uncovering anever-before-described mutationandcracking a vomiting mysteryin these UAB News stories.

10. Diversity in the scientific workforce

[See this section of the talk here]

We know that science, like everything else, is more productive when teams are diverse than if they are all looking the same, Collins said. My number one priority as NIH director is to be sure we are doing everything we can to nurture and encourage the best and brightest to join this effort.

Research diversity at UAB:TheNeuroscience Roadmap Scholars Programat UAB, supported by an NIH R25 grant, is designed to enhance engagement and retention of under-represented graduate trainees in the neuroscience workforce. This is one of several UAB initiatives to increased under-represented groups and celebrate diversity. These include several programs from theMinority Health and Health Disparities Research Centerthat support minority students from the undergraduate level to postdocs; thePartnership Research Summer Training Program, which provides undergraduates and especially minority students with the opportunity to work in UAB cancer research labs; theDeans Excellence Award in Diversityin the School of Medicine; and the newly announcedUnderrepresented in Medicine Senior Scholarship Programfor fourth-year medical students.

Join in:The Roadmap program engages career coaches and peer-to-peer mentors to support scholars. To volunteer your expertise, contact Madison Bamman atmdbamman@uab.eduorvisit the program site.

Learn more:Farah Lubin, Ph.D., associate professor in the Department of Neurobiology and co-director of the Roadmap Scholars Program,shares the words and deeds that can save science careersin this Reporter story. In another story, Upender Manne, Ph.D., professor in the Department of Pathology and a senior scientist in the ONeal Comprehensive Cancer Center, explains how students in the Partnership Research Summer Training Program gethooked on cancer research.

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Looking to the future with Dr. Francis Collins - Newswise

IPS Cell Therapy Comments Off on Looking to the future with Dr. Francis Collins – Newswise | March 17th, 2020

An HIV patient recovered with a stem cell transplant. He became the second patient in the world to recover from this disease.

an HIV patient who received a stem cell transplant is now cured. He has become the second patient in the world to recover from the disease, his doctors announced Tuesday, March 10.

Almost ten years after the first confirmed case of an HIV patient who managed to get rid of it, this second case, known as the London patient, has shown no signs of the virus for 30 months, according to the results published in the journal The Lancet HIV.

In March 2019, Professor Ravindra Gupta, of the University of Cambridge, announced that this man diagnosed with HIV in 2003 was in remission, having shown no sign of the virus for 18 months. The doctor had however called for caution, insisting on the term of remission and not healing, asking for more time.

We suggest that our results represent a cure for HIV

A year later, his team took this step. We suggest that our results represent a cure for HIV, they write, after testing samples of blood, tissue, sperm. We tested a fairly considerable number of places where the virus likes to hide and practically everything was negative, apart from a few fossil remains of non-active virus, Pr Gupta told AFP. It is hard to imagine that all traces of a virus that infects billions of cells have been eliminated, he said.

Like the Berlin patient, the American Timothy Ray Brown considered cured in 2011, this London patient underwent a bone marrow transplant to treat blood cancer, and thus received stem cells from donors carrying a rare genetic mutation that prevents HIV from taking hold, CCR5.

Scientists point out that the procedure used for the two recovered patients is very cumbersome and risky, asking ethical questions, as Professor Gupta points out.

Is the London patient really healed? Asked Sharon Lewin of the University of Melbourne. The data () is of course exciting and encouraging, but in the end, only time will tell, she noted, saying it would take more than a handful of HIV-cured patients to assess the likelihood of a late and unexpected resumption of virus replication .

Almost 38 million people are living with HIV worldwide, but only 62% are receiving triple therapy. Nearly 800,000 people died in 2018 from HIV-related conditions. The emergence of drug-resistant forms of HIV is also a growing concern.

The rest is here:
For the second time in the world, an HIV patient is cured - Medical Progress - Medical Progress

Bone Marrow Stem Cells Comments Off on For the second time in the world, an HIV patient is cured – Medical Progress – Medical Progress | March 16th, 2020

UPDATE:

SPOKANE, Wash. -- Life-saving cells for alocal father of six are on their way to him from Poland. His family has been panicked after a travel ban was put in place by the Polish Government. They say they were told the status of the transport was stalled, and with time slipping away, they needed immediate action.

Jared Weeks was diagnosed withAcute Myeloid Leukemia back in October. His wife Janet contacted 'Help Me Hayley' on Saturday. On Sunday morning, Janet got word that the cells were on their way. She reached out to many government officials and is still trying to sort how and who helped make this happen for her husband.

"I heard that relief in (my husband's) voice and that's all I needed," she said. "I'm so thankful to everyone who shared the story, sent us prayers. I felt it. I really did. People are so overwhelmingly beautiful."

Janet says her husband will have the stem-cell transplant on Tuesday.

"I will be traveling over to Seattle on Monday evening to be there for his 're-birthday,'" she said of the procedure. "I'm so grateful."

PREVIOUS COVERAGE:

SPOKANE, Wash. -- A local father of six desperately needs help receiving life-saving cells provided by an overseas donor. His family says his life depends on it.

His wife Janet sent our Hayley Guenthner this 'Help Me Hayley' request:

"Dear Help Me Hayley,

My children and I are desperate to save my husband. He was diagnosed with Acute Myeloid Leukemia on 10/15/2019 (on his 42nd birthday of all days) since then he has been in the hospital. At the beginning of February we started our journey to the west side of the state to be under the care of Seattle Cancer Care Alliance and to make a long story short, we are now in the transplant stage of his disease.

My husband, Jared Weeks, went inpatient to the University of Washington Medical Center (UWMC) on behalf of the Seattle Cancer Care Alliance. He started his myeloablative chemo regimen on March 10th with the expectation of receiving an Unrelated Allogeneic Peripheral Blood Stem Cell transplant. He had the highest dose of chemotherapy to eliminate his disease and replace his immune system with a 38-year-old female peripheral blood stem cell donation from Poland. Because of the travel ban put in place by the Polish Government in response to the outbreak of the Novel COVID-19 virus, it is becoming impossible to transport these LIFE-SAVING cells that have been extracted from my husband's donor and brought back to the United States. I have left messages for Senator Cathy McMorris-Rodgers, Governor Jay Inslee, Mayor Woodward and Senator Maria Cantwell. I was able to speak personally with State Senator Shelly Short who is passing on this to some of her contacts in the cabinet. I reached out to the Polish Government agency handling the travel ban restrictions and have spoken with an Overseas Citizen Services Safety Officer out of Krakow Poland at the US Embassy-State Department. The travel ban has been put in place but I have been told that roads are still open as well as trains and planes, but as of midnight tonight (not sure if our time or their time) the borders will be closed until March 25th, and maybe extended depending on the COVID-19 outbreak. The cells have been collected from the donor and we are desperate to get them here. Please help us!! God help us.

My husband, Jared Weeks, was diagnosed with Acute Myeloid Leukemia on October 15, 2019 and is in DIRE need of these stem cells to survive.

We need some assistance from the "powers that be" to get these life-saving stem cells to my husband in Washington State ASAP.

His life depnds on it."

There have many people offering to test to see if they are a local match for Jared. Unfortunately, the family doesn't have the kind of time required to find a new donor.

"They would need to go to bethematch.org , however, it is too late in the game to be a donor for Jared but there are hundreds of others that need this life-saving donation as well," Janet said. "The HLA TYPING that is done can take weeks to complete and for Jared, we don't have that kind of time."

Janet is currently in Spokane with their children. She said she is doing everything she can to stay strong for her husband.

"(Jared) is one heck of a dad," Janet said. "He is hardworking, loves the outdoors, fishing, boating and taking his kids on adventures. He is amazing to us and is the center of gravity for our rather large family. He has been through hell and back with this cancer, and is still trusting God completely."

Seattle Cancer Cancer Care Alliance sent KHQ a statement on Jared and other cancer patients relying on life-saving bone marrow transplants during the COVID-19 outbreak.

"The COVID-19 outbreak is an evolving and fluid situation, and the global medical community is collaborating to address the needs of people who are relying on bone marrow transplants for their treatment and survival.

"Seattle Cancer Care Alliance is evaluating every patient who is currently connected with an international or USA-based donor to ensure we have an alternative solution for their treatment should the need arise.

"We are committed to continuing to coordinate with the National Marrow Donor Program and the World Marrow Donor Association, along with donor representatives in various countries, to prevent potential disruptions of critical medical transport so that every cancer patient has access to the life-saving treatment they need.

"SCCA is dedicated to providing the highest-quality cancer care, and we take that responsibility very seriously. We continue to work very closely with our alliance partners -Fred Hutch, UW Medicine and Seattle Childrens- and sharing our approach and best practices with other transplant centers around the country who may face similar unprecedented challenges."

See the article here:
HELP ME HAYLEY: Spokane father of six receiving life-saving cells from Poland donor - KHQ Right Now

Bone Marrow Stem Cells Comments Off on HELP ME HAYLEY: Spokane father of six receiving life-saving cells from Poland donor – KHQ Right Now | March 16th, 2020

By: Cobey Bartels

Date: 16.03.2020

Friend of Owner//Driver and owner of the iconic Filthy White 4000 we covered last year, Mick Moo Lake, was diagnosed with cancer on Christmas Eve.

Mick and Mel Lake, with 'Filthy'

Since the devastating news, Mick and his wife Mel have been struggling to balance treatment and operating their business Truckin Stainless setting up a GoFundMe page to help cover the costs of hospital care.

Mick has Double Myeloma, a form of cancer that develops from plasma cells in the bone marrow, and has been receiving ongoing treatment since New Years Eve.

In 10 weeks Mick is having a Stem Cell Blood Transfusion, which will put him out of work for at least a month and will put significant strain on his business and familys livelihood.

At the time of writing, the GoFundMe page has raised $3,195 and Mick and Mel say the money will go towards covering the cost of treatment and help keep their business afloat.

Mick has been working through the treatment, where possible, to keep Truckin Stainless kicking along with the help of his good mate Steve who travelled down from Mackay to help lighten the load.

"He heard about what was going on when he was down here at the time, and he decided to stay and help while I was getting treatment," Mick says.

"Ive been working through it, going to hospital for treatments then back to the workshop - i havent stopped.

"In respect of all the wonderful people that have had to endure this terrible disease, we understand that asking for donations seems a bit steep, but if you would like to donate please do so, or think to donate to any cancer foundation," he says.

You can donate or find out more HERE.

You can also follow our updates by liking us on Facebook.

Trucks For Hire | Forklifts For Hire | Cranes For Hire | Generators For Hire | Transportable Buildings For Hire

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Moo trucks on through cancer battle - Owner//Driver

Bone Marrow Stem Cells Comments Off on Moo trucks on through cancer battle – Owner//Driver | March 16th, 2020

Global Autologous Stem Cell Based Therapies Market Report is a professional and in-depth research report on the worlds major regional market conditions of the Autologous Stem Cell Based Therapies industry, focusing on the main regions and the main countries (United States, Europe, Japan and China).

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Autologous Stem Cell Based Therapies Market 2020: Potential Growth, Challenges, Attractive Valuation | Key Players: Anterogen, Holostem Advanced...

Cardiac Stem Cells Comments Off on Autologous Stem Cell Based Therapies Market 2020: Potential Growth, Challenges, Attractive Valuation | Key Players: Anterogen, Holostem Advanced… | March 16th, 2020

SEATTLE--(BUSINESS WIRE)--NanoSurface Biomedical announced today that it has executed an exclusive IP license agreement related to innovative heart-on-chip technology developed by researchers at the University of Washington (UW). An experimental system built from the same heart-on-chip technology was launched into space on Friday, March 6, 2020 at 11:50 PM EST aboard SpaceX's 20th resupply mission to the International Space Station (ISS) as part of the Tissue Chips in Space initiative conducted in partnership between the National Center for Advancing Translational Sciences (NCATS) and the ISS U.S. National Laboratory (ISS National Lab). NanoSurface will commercialize the heart-on-chip platform for use by pharmaceutical companies in preclinical drug development.

The heart-on-chip system will spend 30 days aboard the ISS as part of a series of experiments intended to study the effects of microgravity on human cells and tissues. In space we are using the heart-on-chip system in microgravity conditions to help improve our understanding of the aging process and cardiac biology, but this heart-on-chip system also has enormous potential for accelerating the discovery of new medicines back here on Earth, said Deok-Ho Kim, an Associate Professor of biomedical engineering and medicine at Johns Hopkins University, the principal investigator for the heart-on-chip experiment aboard the ISS, and the scientific founder of NanoSurface Bio.

The heart-on-chip platform uses three-dimensional engineered cardiac tissues (3D ECTs) grown from human cardiomyocytes, or beating heart cells, derived from induced pluripotent stem cells (iPSCs). As the 3D ECTs beat, researchers can measure the amount of force generated by each contraction, and then evaluate how that force changes after treating the tissues with candidate drugs. 3D ECTs can be made from cells from either healthy individuals or individuals with diseases, offering great promise in predictive preclinical testing of candidate drugs for safety and efficacy.

I am incredibly excited that the talented team at NanoSurface will be carrying this technology forward for use in the drug development industry, said Nathan Sniadecki, one of the inventors of the heart-on-chip technology and a professor of mechanical engineering at UW. Last year, Professor Sniadecki joined NanoSurfaces board of scientific advisors to guide the commercial development of the technology.

NanoSurface Bios execution of this exclusive license adds significant value to the portfolio of IP it has already licensed from researchers at UW. It is well recognized that the drug development process is extremely slow and expensive. At NanoSurface we are eager to develop technologies that enable the use of human iPSC-derived cells and tissues in preclinical drug development, ultimately leading to better prediction of how drugs will affect patients in the clinic, lowering costs, and speeding life-saving medicines to market, said NanoSurface CEO Michael Cho.

About NanoSurface Biomedical

NanoSurface Biomedical is a biotechnology company based in Seattle, WA that develops stem cell-based assay technologies to accelerate drug development. NanoSurfaces structurally matured cardiac tissue models, assay instruments, and discovery services leverage human stem cell technology to help pharmaceutical companies predictively assess the safety and efficacy of candidate drugs early during preclinical development. NanoSurfaces mission is to help bring life-saving medicines to market in less time and at lower cost. To learn more, visit http://www.nanosurfacebio.com.

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NanoSurface Bio Executes Exclusive License of Heart-on-Chip Technology Launched Into Space - Business Wire

Cardiac Stem Cells Comments Off on NanoSurface Bio Executes Exclusive License of Heart-on-Chip Technology Launched Into Space – Business Wire | March 15th, 2020

Immune cells by fluorescence microscopy: Blood stem cells remember a previous attack and produce more immune cells like these macrophages to fight a new infection. Credit: Sieweke lab/CIML

These findings should have a significant impact on future vaccination strategies and pave the way for new treatments of an underperforming or over-reacting immune system. The results of this research are published in Cell Stem Cell on March 12, 2020.

Stem cells in our bodies act as reservoirs of cells that divide to produce new stem cells, as well as a myriad of different types of specialized cells, required to secure tissue renewal and function. Commonly called blood stem cells, the hematopoietic stem cells (HSC) are nestled in the bone marrow, the soft tissue that is in the center of large bones such as the hips or thighs. Their role is to renew the repertoire of blood cells, including cells of the immune system which are crucial to fight infections and other diseases.

Until a decade ago, the dogma was that HSCs were unspecialized cells, blind to external signals such as infections. Only their specialized daughter cells would sense these signals and activate an immune response. But work from Prof. Michael Siewekes laboratory and others over the past years has proven this dogma wrong and shown that HSCs can actually sense external factors to specifically produce subtypes of immune cells on demand to fight an infection. Beyond their role in an emergency immune response, the question remained as to the function of HSCs in responding to repeated infectious episodes. The immune system is known to have a memory that allows it to better respond to returning infectious agents. The present study now establishes a central role for blood stem cells in this memory.

We discovered that HSCs could drive a more rapid and efficient immune response if they had previously been exposed to LPS, a bacterial molecule that mimics infection, said Dr. Sandrine Sarrazin, Inserm researcher and senior-author of the publication. Prof. Michael Sieweke, Humboldt Professor at TU Dresden, CNRS Research Director and last author of the publication, explained how they found the memory was stored within the cells: The first exposure to LPS causes marks to be deposited on the DNA of the stem cells, right around genes that are important for an immune response. Much like bookmarks, the marks on the DNA ensure that these genes are easily found, accessible and activated for a rapid response if a second infection by a similar agent was to come.

The authors further explored how the memory was inscribed on the DNA, and found C/EBP? to be the major actor, describing a new function for this factor, which is also important for emergency immune responses. Together, these findings should lead to improvements in tuning the immune system or better vaccination strategies.

The ability of the immune system to keep track of previous infections and respond more efficiently the second time they are encountered is the founding principle of vaccines. Now that we understand how blood stem cells bookmark immune response circuits, we should be able to optimize immunization strategies to broaden the protection to infectious agents. It could also more generally lead to new ways to boost the immune response when it underperforms or turn it off when it overreacts, concluded Prof. Michael Sieweke.

The research group of Prof. Michael Sieweke works at the interface of immunology and stem cell research. The scientists focus on the study of hematopoietic stem cells and macrophages, long-lived mature cells of the immune system that fulfil an important role in tissue regeneration. In 2018, Prof. Michael Sieweke received the most valuable research award in Germany: the Alexander von Humboldt Professorship, which brings top international researchers to German universities. In addition to his position as Research Director at the Centre for Immunology at the University of Marseille Luminy, he now acts as Deputy Director at the Center for Regenerative Therapies at TU Dresden (CRTD). CRTD is academic home for scientists from more than 30 nations. Their mission is to discover the principles of cell and tissue regeneration and leveraging this for recognition, treatment and reversal of diseases. The CRTD links the bench to the clinic, scientists to clinicians to pool expertise in stem cells, developmental biology, gene-editing and regeneration towards innovative therapies for neurodegenerative diseases such as Alzheimers and Parkinsons disease, hematological diseases such as leukaemia, metabolic diseases such as diabetes, retina and bone diseases.

Reference: C/EBP-Dependent Epigenetic Memory Induces Trained Immunity in Hematopoietic Stem Cells by Brengre de Laval, Julien Maurizio, Prashanth K. Kandalla, Gabriel Brisou, Louise Simonnet, Caroline Huber, Gregory Gimenez, Orit Matcovitch-Natan, Susanne Reinhardt, Eyal David, Alexander Mildner, Achim Leutz, Bertrand Nadel, Christophe Bordi, Ido Amit, Sandrine Sarrazin and Michael H.Sieweke, 12 March 2020, Cell Stem Cell.DOI: 10.1016/j.stem.2020.01.017

This study was funded by TU Dresden / CRTD through the German Excellence Initiative, the German Research Foundation as well as through an ERC Advanced Grant from the European Research Council and the Alexander von Humboldt Foundation. The study was further supported by funding from the Institut National de la Sante et de la Recherche Medicale, the Centre National de la Recherche Scientifique, Aix-Marseille University, the Agence Nationale de la Recherche, the Foundation ARC pour la Recherche sur le Cancer, an INSERM-Helmholtz cooperation programme and the Einstein Foundation.

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Newly Discovered Memory in Our Bones: Keeping a Record of Previous Infections to Boost Immunity - SciTechDaily

Bone Marrow Stem Cells Comments Off on Newly Discovered Memory in Our Bones: Keeping a Record of Previous Infections to Boost Immunity – SciTechDaily | March 15th, 2020

Revolutionary Gene-Editing Tool

Cardiovascular or heart disease (CVDs) is the leading cause of death across the world. Heart attacks resulting due to CVDs can cause death, and severe damage to cardiac muscle a muscle that forms the wall of the heart in survivors. However, researchers claim that they have discovered stem-cell activated mechanisms that promote healing after a heart attack.

According to the study by researchers from Mayo Clinic, stem cells were found to reverse the damage and restore cardiac muscle back to its condition before a heart attack. Human cardiopoietic cells obtained from stem cells within the bone marrow were found to hone in on damaged proteins and reverse intricate changes that a heart attack caused.

"The response of the diseased heart to cardiopoietic stem cell treatment revealed development and growth of new blood vessels, along with new heart tissue," said Dr. Kent Arrell, first author of the study, in a statement.

For the study, the researchers examined the diseased hearts of mice. The hearts of mice that received human cardiopoietic stem cell therapy were compared with those of that did not. Nearly 4,000 cardiac proteins were identified using a data science technique to map proteins found in the cardiac muscle. Over 10 per cent of the discovered proteins were found to suffer damage as a result of a heart attack.

"While we anticipated that the stem cell treatment would produce a beneficial outcome, we were surprised how far it shifted the state of diseased hearts away from disease and back toward a healthy, pre-disease state," said Dr. Arrell.

While the organs in the human body have the ability to repair their damaged cells, they may be unable to restore the loss entirely, and this holds good for cardiac cells as well. Dr. Andre Terzic, senior author of the study, said: "The extent of change caused by a heart attack is too great for the heart to repair itself or to prevent further damage from occurring."

He explained that upon the administration of cardiopoietic stem cell therapy to mice, a partial or complete reversal of nearly two-thirds of the damage caused by a heart attack was noted. Around 85 per cent of all cellular functional categories struck by the disease responded favorably to the treatment.

According to the World Health Organisation (WHO), CVDs claim nearly 18 million lives every year, which translates to 31 per cent of all deaths. The findings of the study provide an improved understanding of the restoration of heart health using stem cells and provide a framework for wider utilization of stem cell therapy for the treatment of various conditions.

Stressing that the actual mechanism behind the repair of diseased organs by stem cells is poorly understood, Dr. Terzic added: "This study sheds light on the most intimate, yet comprehensive, regenerative mechanisms paving a road map for responsible and increasingly informed stem cell application."

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Stem cells can reverse damage caused by heart attack; repair mechanism discovered: Study - International Business Times, Singapore Edition

Bone Marrow Stem Cells Comments Off on Stem cells can reverse damage caused by heart attack; repair mechanism discovered: Study – International Business Times, Singapore Edition | March 15th, 2020

The novel coronavirus disease 2019 (COVID-19) has grown to become a global public health emergency. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases. A new study offers a promising pathway for developing such a treatment.

The new approach involves intravenous transplantation of mesenchymal stem cells (MSCs) into the patients. It was successfully tested in 7 COVID-19 patients, in Beijing YouAn Hospital, Capital Medical University, China. The results are published in the scientific journal Aging and Disease, entitled "Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia".

http://www.aginganddisease.org/article/0000/2152-5250/ad-0-0-216.shtml

The study was conducted by a team led by Dr. Robert Chunhua Zhao, with Shanghai University and Chinese Academy of Medical Sciences & Peking Union Medical College, China.

Moreover the study was reviewed by a scientific committee of the International Society on Aging and Disease (ISOAD) and the recently established UNESCO-affiliated committee on Anti-Aging and Disease Prevention http://www.aginganddisease.org/article/2020/2152-5250/ad-11-1-212.shtml

Based on the 14 days observation, MSCs could cure or significantly improve the functional outcomes of all the seven tested patients without observed adverse effects, contrary to 3 controls. The pulmonary function and symptoms of these seven patients were significantly improved after MSC transplantation. Among them, one severe and two common patients recovered and were discharged in 10 days after the treatment. The improvement was particularly dramatic for an elderly (65 y.o.) male patient in severe critical condition. All of his primary and secondary outcomes improved: the inflammation status, the oxygen saturation, and the functional biochemical indicators returned to normal reference values in 2~4 days after the treatment.

The presented evidence suggests that the therapeutic effects are based on the immunomodulatory capacity of mesenchymal stem cells (restoring the balance of the immune system). The coronavirus infection can stimulate a terrible cytokine storm in the lung, disrupting the balance of cytokines (signaling molecules of the immune system) such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A and TNF cytokines, followed by the edema, dysfunction of the air exchange, acute respiratory distress syndrome, acute cardiac injury and the secondary infection, which may lead to death. The bone-marrow derived MSCs could inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment, thus they could represent a safe and effective treatment for patients with COVID-19 pneumonia, especially for the patients in critically severe conditions. A larger validation study is required and is already underway, yet the initial results are encouraging.

Notably, the coronavirus-infected pneumonia is more likely to affect older individuals, especially older males, with comorbidities, resulting in their severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In other words, aging appears to be the main risk factor for bad outcomes. However, the cure essentially depends on the patient's own immune system. When the overactivated immune system kills the virus, it produces a large number of inflammatory factors, leading to the severe cytokine storms. This suggests that the main reason for the organs damage may be the virus-induced cytokine storm. Older subjects may be much easier to be affected due to immunosenescence. The study showed remarkable recovery of the elderly patients thanks to restoring their immune function.

Thus, the study may have a broader significance, even beyond the treatment of the severe coronavirus disease. This study exemplifies that the general therapeutic improvement of the immune system in the elderly can improve outcome and survival, which may have more general relevance for other aging-related communicable diseases. Thus, this study may inspire and pave the way for further promising directions to investigate the connection between aging and disease, and to treat both communicable and non-communicable aging-related diseases.

The Romanian journalist Laura tefnu spoke with Dr. Ilia Stambler about the broader implications of this research. Ilia Stambler is a co-author in this study who was involved in the study review, interpretation and discussion. He serves as the Outreach Coordinator of the International Society on Aging and Disease (ISOAD) and Director of Research and Development at Shmuel Harofe Geriatric Medical Center in Israel.

Q: How does it feel to be part of the team which discovered a groundbreaking treatment for what is currently considered one of the biggest global challenges?

A: I feel very honored to be included in this extended international team. I hope this team continues its work that will also involve additional collaborations.

Q: As a researcher, what did you find most interesting about this novel coronavirus? What seems most threatening about this new virus?

A: The spreading ability of this virus is relatively high and it has the capacity to affect the entire global population. This is what makes this virus a particularly strong concern for global public health. The social effects of this epidemic are also of great importance. In a sense, this virus is testing the strength of our public health systems. Will the immunity of our public healthcare be strong enough to contain it? I hope it is.

Q: Did the discovery of this groundbreaking new therapeutic approach make you more optimistic (when it comes to containing and limiting the damage of Covid-19)? In which sense (where was your optimism before the discovery)?

A: I was optimistic before, as I believe that, same as for many infectious diseases in the past, also for this disease, effective therapeutic and preventive measures will be found and used. This work further increased my optimism. Of course, this is an initial study, and this is only one of the potential means in the therapeutic, preventive and hygienic arsenal. More research and confirmation will be needed. Yet, even at this stage, the clear positive result of this study shows that it is indeed possible to improve the outcomes for COVID-19 patients even in severe conditions. Moreover, it gives more hope that effective treatments can be sought and found also for other aging-related infectious diseases and conditions.

Q: Is there an explanation regarding the reasons why Covid-19 seems to pardon children and affects the most elder individuals, especially men?

A: There is yet no clear or fully agreed explanation. But a plausible cause may be due to the so called immuno-senescence phenomenon, or the inability of the aging immune system to cope with new threats and restore the immune balance following the infection. In men the immuno-senescence effects are often more strongly present than in women. Thus, aging appears to be the main risk factor for this disease and if we really wish to defeat this epidemic, we need to address this main risk factor, in other words, we need to therapeutically intervene and ameliorate the degenerative aging process. The proposed mesenchymal stem cell therapy shows the so-called immuno-modulation effects or the ability to generally improve the immune system, help restore the immune balance after disturbances, especially for the elderly. And this can be the more general explanation for its effects against the aging-related COVID-19 pneumonia, as well as potentially other aging-related diseases.

Q: How did you manage to find so fast a treatment that is responding so well?

A: The mesenchymal stem cell treatment has been researched and developed by Dr. Zhao and his team for many years, and indicated positive effects for multiple health conditions. It is exactly because of the common and critical role of the immune system impairment in all these conditions, that the treatment developed by Dr. Zhaos team was already in place and could be immediately used also for this condition dependent on the immune function. Moreover, the success of this therapy against COVID-19 can further boost the research and therapy of other immunity-dependent health conditions and diseases, especially aging-related diseases, due to the common mechanisms of action.

Q: How may this discovery change the game?

A: Unlike other public health measures, like quarantine and hygiene, that can be very quickly applied, the research, development, regulatory approval and application of new therapies is a much slower process. So we should first of all apply the public health measures to contain the epidemic. But the hope is that this therapy will undergo further research and validation as soon as possible, and in case of validated efficacy and safety, will be used in as many patients who need it as possible, as soon as possible. That is exactly why we need to accelerate the research, development and application of promising new therapies. When the new therapy enters wide clinical practice, there are grounds to believe it can improve the health and even save the lives of many patients, not only suffering from COVID-19, but also other conditions.

Q: Which was the response/reaction of authorities after you published the results of your research?

A: The outreach to the authorities in several countries has only started. Moreover, the study is only initial and it is too early to make policy recommendations. A larger validation study is required. Yet, if there is even a slight possibility this could become a life-saving therapy for COVID-19 patients and others, this opportunity should not be missed by the decision makers.

Q: Some treatments are more expensive than others. Will the treatment you discovered be accessible to people, or the cost for producing it will limit its accessibility?

A: The cells for this treatment can be mass produced and can be rather affordable. Of course, the actual price will depend both on the scale of production and pricing policies. And this is already a question that goes beyond pure technology, but becomes a question about the social means to make new therapies available to all. This should also be a crucial part of the public discussion about the social need to promote the rapid research and development as well as broad application of new therapies that are proven to be safe and effective.

Q: Which are the best measures a country can take to limit the spread and the consequences of the novel coronavirus?

The usual quarantine and public hygiene measures are the most feasible and effective: minimization of large gatherings, minimization of travel, cleanliness. We should hope and work for new effective therapies to arrive as soon as possible. But so far public health measures are the most effective and feasible.

Ilia Stambler is an IEET Affiliate Scholar. He completed his PhD degree at the Department of Science, Technology and Society, Bar-Ilan University. His thesis subject, and his main interest, is the History of Life-extensionism in the 20th Century.

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A new therapeutic approach against COVID-19 Pneumonia - Institute for Ethics and Emerging Technologies

Cardiac Stem Cells Comments Off on A new therapeutic approach against COVID-19 Pneumonia – Institute for Ethics and Emerging Technologies | March 14th, 2020

New York, March 13, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Induced Pluripotent Stem Cells Market: Global Industry Analysis, Trends, Market Size, and Forecasts up to 2025" - https://www.reportlinker.com/p05874276/?utm_source=GNW 6% over the forecast period from 2019-2025. The study on induced pluripotent stem cells market covers the analysis of the leading geographies such as North America, Europe, Asia-Pacific, and RoW for the period of 2017 to 2025.

The report on induced pluripotent stem cells market is a comprehensive study and presentation of drivers, restraints, opportunities, demand factors, market size, forecasts, and trends in the global induced pluripotent stem cells market over the period of 2017 to 2025. Moreover, the report is a collective presentation of primary and secondary research findings.

Porters five forces model in the report provides insights into the competitive rivalry, supplier and buyer positions in the market and opportunities for the new entrants in the global induced pluripotent stem cells market over the period of 2017 to 2025. Further, IGR- Growth Matrix gave in the report brings an insight into the investment areas that existing or new market players can consider.

Report Findings1) Drivers Increased government fundings and rising industry focus on the development of novel therapies Rising interest in stem cell therapy2) Restraints High the cost associated with storage3) Opportunities Growing applications of iPS cells in several biopharmaceutical applications provides extensive potential to the key players in the market

Research Methodology

A) Primary ResearchOur primary research involves extensive interviews and analysis of the opinions provided by the primary respondents. The primary research starts with identifying and approaching the primary respondents, the primary respondents are approached include1. Key Opinion Leaders associated with Infinium Global Research2. Internal and External subject matter experts3. Professionals and participants from the industry

Our primary research respondents typically include1. Executives working with leading companies in the market under review2. Product/brand/marketing managers3. CXO level executives4. Regional/zonal/ country managers5. Vice President level executives.

B) Secondary ResearchSecondary research involves extensive exploring through the secondary sources of information available in both the public domain and paid sources. At Infinium Global Research, each research study is based on over 500 hours of secondary research accompanied by primary research. The information obtained through the secondary sources is validated through the crosscheck on various data sources.

The secondary sources of the data typically include1. Company reports and publications2. Government/institutional publications3. Trade and associations journals4. Databases such as WTO, OECD, World Bank, and among others.5. Websites and publications by research agencies

Segment CoveredThe global induced pluripotent stem cells market is segmented on the basis of derived cell type, application, and end user.

The Global Induced Pluripotent Stem Cells Market by Derived Cell Type Fibroblasts Amniotic Cells Hepatocytes Keratinocytes Others

The Global Induced Pluripotent Stem Cells Market by Application Drug Development Regenerative Medicine Toxicity Testing Academic Research

The Global Induced Pluripotent Stem Cells Market by End User Research Organizations Hospitals Biopharma Industries

Company Profiles Astellas Pharma Inc. Fate Therapeutics Inc. FUJIFILM Holdings Corporation Evotec SE Japan Tissue Engineering Co., Ltd ViaCyte, Inc. Vericel Corporation Bristol-Myers Squibb Company Aastrom Biosciences, Inc. Acelity Holdings, Inc.

What does this report deliver?1. Comprehensive analysis of the global as well as regional markets of the induced pluripotent stem cells market.2. Complete coverage of all the segments in the induced pluripotent stem cells market to analyze the trends, developments in the global market and forecast of market size up to 2025.3. Comprehensive analysis of the companies operating in the global induced pluripotent stem cells market. The company profile includes analysis of product portfolio, revenue, SWOT analysis and latest developments of the company.4. IGR- Growth Matrix presents an analysis of the product segments and geographies that market players should focus to invest, consolidate, expand and/or diversify.Read the full report: https://www.reportlinker.com/p05874276/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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Global induced pluripotent stem cells market is expected to grow with a CAGR of 8.6% over the forecast period from 2019-2025 - GlobeNewswire

IPS Cell Therapy Comments Off on Global induced pluripotent stem cells market is expected to grow with a CAGR of 8.6% over the forecast period from 2019-2025 – GlobeNewswire | March 13th, 2020

In a talk at UAB on March 6, the NIH director shared his thoughts on exceptional opportunities for science and young scientists and highlighted several exciting UAB projects.

NIH Director Francis Collins, M.D., Ph.D., visited UAB on March 6. In addition to his public talk, Collins had breakfast with UAB medical students and met with groups of young researchers and other investigators across campus.Speaking to a packed University of Alabama at Birmingham audience March 6, Francis Collins, M.D., Ph.D., director of the National Institutes of Health, shared his picks of 10 areas of particular excitement and promise in biomedical research.

In nearly every area, UAB scientists are helping to lead the way as Collins himself noted in several cases. At the conclusion of his talk, Collins addedhis advice for young scientists. Here is Collins top 10 list, annotated with some of the UAB work ongoing in each area and ways that faculty, staff and students can get involved.

I am so jazzed with what has become possible with the ability to study single cells and see what they are doing, Collins said. They have been out of our reach now we have reached in. Whether you are studying rheumatoid arthritis, diabetes or the brain, you have the chance to ask each cell what it is doing.

Single-cell sequencing and UAB:Collins noted that Robert Carter, M.D., the acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was a longtime faculty member at UAB (serving as director of the Division of Clinical Immunology and Rheumatology). For the past several years, UAB researchers have been studying gene expression in subpopulations of immune cells inpatients with rheumatoid arthritis.

Join in:Researchers can take advantage of the single-cell sequencing core facility in UABsComprehensive Flow Cytometry Core, directed by John Mountz, M.D., Ph.D., Goodwin-Blackburn Research Chair in Immunology and professor in the Department of Medicine Division of Clinical Immunology and Rheumatology.

Learn more:Mountz and other heavy users of single-cell sequencing explain how the techniqueslet them travel back in time and morein this UAB Reporter story.

The NIHsBRAIN Initiativeis making this the era where we are going to figure out how the brain works all 86 billion neurons between your ears, Collins said. The linchpin of this advance will be the development of tools to identify new brain cell types and circuits that will improve diagnosis, treatment and prevention of autism, schizophrenia, Parkinsons and other neurological conditions, he said.

Brain tech and UAB:Collins highlighted thework of BRAIN Initiative granteeHarrison Walker, M.D., an associate professor in the Department of Neurology, whose lab has been developing a more sophisticated way to understand the benefits of deep brain stimulation for people with Parkinsons and maybe other conditions, Collins said.

Join in:UABs planned new doctoral program in neuroengineering would be the first of its kind in the country.

Learn more:Find out why neuroengineering is asmart career choicein this UAB Reporter story.

Researchers can now take a blood cell or skin cell and, by adding four magic genes, Collins explained, induce the cells to become stem cells. These induced pluripotent stem (iPS) cells can then in turn be differentiated into any number of different cell types, including nerve cells, heart muscle cells or pancreatic beta cells. The NIH has invested in technology to put iPS-derived cells on specialized tissue chips. Youve got you on a chip, Collins explained. Some of us dream of a day where this might be the best way to figure out whether a drug intervention is going to work for you or youre going to be one of those people that has a bad consequence.

iPS cells at UAB:Collins displayed images of thecutting-edge cardiac tissue chipdeveloped by a UAB team led by Palaniappan Sethu, Ph.D., an associate professor in the Department of Biomedical Engineering and the Division of Cardiovascular Disease. The work allows the development of cardiomyocytes that can be used to study heart failure and other conditions, Collins said.

Join in:UABs biomedical engineering department, one of the leading recipients of NIH funding nationally, is a joint department of the School of Engineering and School of Medicine. Learn more about UABsundergraduate and graduate programs in biomedical engineering, and potential careers, here.

Learn more:See howthis novel bioprinterdeveloped by UAB biomedical researchers is speeding up tissue engineering in this story from UAB News.

We have kind of ignored the fact that we have all these microbes living on us and in us until fairly recently, Collins said. But now it is clear that we are not an organism we are a superorganism formed with the trillions of microbes present in and on our bodies, he said. This microbiome plays a significant role not just in skin and intestinal diseases but much more broadly.

Microbiome at UAB:Collins explained that work led by Casey Morrow, Ph.D., and Casey Weaver, M.D., co-directors of theMicrobiome/Gnotobiotics Shared Facility, has revealed intriguing information abouthow antibiotics affect the gut microbiome. Their approach has potential implications for understanding, preserving and improving health, Collins said.

Join in:Several ongoing clinical trials at UAB are studying the microbiome, including a studymodifying diet to improve gut microbiotaand an investigation of the microbiomes ofpostmenopausal women looking for outcomes and response to estrogen therapy.

Learn more:This UAB News storyexplains the UAB researchthat Collins highlighted.

Another deadly influenza outbreak is likely in the future, Collins said. What we need is not an influenza vaccine that you have to redesign every year, but something that would actually block influenza viruses, he said. Is that even possible? It just might be.

Influenza research at UAB:Were probably at least a decade away from a universal influenza vaccine. But work ongoing at UAB in the NIH-fundedAntiviral Drug Discovery and Development Center(AD3C), led by Distinguished Professor Richard Whitley, M.D., is focused on such an influenza breakthrough.

Join in:For now, the most important thing you can do to stop the flu is to get a flu vaccination. Employees can schedule afree flu vaccination here.

Learn more:Why get the flu shot? What is it like? How can you disinfect your home after the flu? Get all the information atthis comprehensive sitefrom UAB News.

The NIH has a role to play in tackling the crisis of opioid addiction and deaths, Collins said. The NIHs Helping to End Addiction Long-term (HEAL) initiative is an all-hands-on-deck effort, he said, involving almost every NIH institute and center, with the goal of uncovering new targets for preventing addiction and improving pain treatment by developing non-addictive pain medicines.

Addiction prevention at UAB:A big part of this initiative involves education to help professionals and the public understand what to do, Collins said. The NIH Centers of Excellence in Pain Education (CoEPE), including one at UAB, are hubs for the development, evaluation and distribution of pain-management curriculum resources to enhance pain education for health care professionals.

Join in:Find out how to tell if you or a loved one has a substance or alcohol use problem, connect with classes and resources or schedule an individualized assessment and treatment through theUAB Medicine Addiction Recovery Program.

Learn more:Discover some of the many ways that UAB faculty and staff aremaking an impact on the opioid crisisin this story from UAB News.

We are all pretty darn jazzed about whats happened in the past few years in terms of developing a new modality for treating cancer we had surgery, we had radiation, we had chemotherapy, but now weve got immunotherapy, Collins said.

Educating immune system cells to go after cancer in therapies such as CAR-T cell therapy is the hottest science in cancer, he said. I would argue this is a really exciting moment where the oncologists and the immunologists together are doing amazing things.

Immunotherapy at UAB:I had to say something about immunology since Im at UAB given that Max Cooper, whojust got the Lasker Awardfor [his] B and T cell discoveries, was here, Collins said. This is a place I would hope where lots of interesting ideas are going to continue to emerge.

Join in:The ONeal Comprehensive Cancer Center at UAB is participating in a number of clinical trials of immunotherapies.Search the latest trials at the Cancer Centerhere.

Learn more:Luciano Costa, M.D., Ph.D., medical director of clinical trials at the ONeal Cancer Center, discusses the promise ofCAR-T cell therapy in this UAB MedCast podcast.

Assistant Professor Ben Larimer, Ph.D., is pursuing a new kind of PET imaging test that could give clinicians afast, accurate picture of whether immunotherapy is workingfor a patient in this UAB Reporter article.

The All of Us Research Program from NIH aims to enroll a million Americans to move away from the one-size-fits-all approach to medicine and really understand individual differences, Collins said. The program, which launched in 2018 and is already one-third of the way to its enrollment goal, has a prevention rather than a disease treatment approach; it is collecting information on environmental exposures, health practices, diet, exercise and more, in addition to genetics, from those participants.

All of Us at UAB:UAB has been doing a fantastic job of enrolling participants, Collins noted. In fact, the Southern Network of the All of Us Research Program, led by UAB, has consistently been at the top in terms of nationwide enrollment, as School of Medicine Dean Selwyn Vickers, M.D., noted in introducing Collins.

Join in:Sign up forAll of Usat UAB today.

Learn more:UABs success in enrolling participants has led to anew pilot study aimed at increasing participant retention rates.

Rare Disease Day, on Feb. 29, brought together hundreds of rare disease research advocates at the NIH, Collins said. NIH needs to play a special role because many diseases are so rare that pharmaceutical companies will not focus on them, he said. We need to find answers that are scalable, so you dont have to come up with a strategy for all 6,500 rare diseases.

Rare diseases at UAB: The Undiagnosed Diseases Network, which includes aUAB siteled by Chief Genomics Officer Bruce Korf, M.D., Ph.D., is a national network that brings together experts in a wide range of conditions to help patients, Collins said.

Participants in theAlabama Genomic Health Initiative, also led by Korf, donate a small blood sample that is tested for the presence of specific genetic variants. Individuals with indications of genetic disease receive whole-genome sequencing. Collins noted that lessons from the AGHI helped guide development of the All of Us Research Program.

Collins also credited UABs Tim Townes, Ph.D., professor emeritus in the Department of Biochemistry and Molecular Genetics, for developing the most significantly accurate model of sickle cell disease in a mouse which has been a great service to the [research] community. UAB is now participating in anexciting clinical trial of a gene-editing technique to treat sickle cellalong with other new targeted therapies for the devastating blood disease.

Join in:In addition to UABs Undiagnosed Diseases Program (which requires a physician referral) and the AGHI, patients and providers can contact theUAB Precision Medicine Institute, led by Director Matt Might, Ph.D. The institute develops precisely targeted treatments based on a patients unique genetic makeup.

Learn more:Discover how UAB experts solved medical puzzles for patients by uncovering anever-before-described mutationandcracking a vomiting mysteryin these UAB News stories.

We know that science, like everything else, is more productive when teams are diverse than if they are all looking the same, Collins said. My number one priority as NIH director is to be sure we are doing everything we can to nurture and encourage the best and brightest to join this effort.

Research diversity at UAB:TheNeuroscience Roadmap Scholars Programat UAB, supported by an NIH R25 grant, is designed to enhance engagement and retention of under-represented graduate trainees in the neuroscience workforce. This is one of several UAB initiatives to increased under-represented groups and celebrate diversity. These include several programs from theMinority Health and Health Disparities Research Centerthat support minority students from the undergraduate level to postdocs; thePartnership Research Summer Training Program, which provides undergraduates and especially minority students with the opportunity to work in UAB cancer research labs; theDeans Excellence Award in Diversityin the School of Medicine; and the newly announcedUnderrepresented in Medicine Senior Scholarship Programfor fourth-year medical students.

Join in:The Roadmap program engages career coaches and peer-to-peer mentors to support scholars. To volunteer your expertise, contact Madison Bamman atmdbamman@uab.eduorvisit the program site.

Learn more:Farah Lubin, Ph.D., associate professor in the Department of Neurobiology and co-director of the Roadmap Scholars Program,shares the words and deeds that can save science careersin this Reporter story. In another story, Upender Manne, Ph.D., professor in the Department of Pathology and a senior scientist in the ONeal Comprehensive Cancer Center, explains how students in the Partnership Research Summer Training Program gethooked on cancer research.

In answer to a students question, Collins also shared his advice to young scientists. One suggestion: Every investigator needs to be pretty comfortable with some of the computational approaches to science, Collins said. Big data is here artificial intelligence, machine-learning. We can all get into that space. But its going to take some training, and it will be really helpful to have those skills.

Join in:UAB launched aMaster of Science in Data Scienceprogram in fall 2018.

Learn more:Discover how UAB researchers areusing machine-learning in their labsand toimprove cancer treatment. Those looking for a free introduction cantake advantage of the Data Science Clubfrom UAB IT Research Computing.

Link:
Looking to the future with Dr. Francis Collins - UAB News

Skin Stem Cells Comments Off on Looking to the future with Dr. Francis Collins – UAB News | March 13th, 2020

Barth syndromeis a rare metabolic disease caused by mutation of a gene calledtafazzinorTAZ. It can cause life-threatening heart failure and also weakens the skeletal muscles, undercuts the immune response, and impairs overall growth. Because Barth syndrome is X-linked, it almost always occurs in boys. There is no cure or specific treatment.

In 2014, to get a better understanding of the disease,William Pu, MD, and colleagues at Boston Childrens Hospital collaborated with the Wyss Institute to create a beatingheart on a chip model of Barth syndrome. The model used heart-muscle cells with theTAZmutation, derived from patients own skin cells.It showedthatTAZis truly at the heart of cardiac dysfunction: the heart muscle cells did not assemble normally, mitochondria inside the cells were disorganized, and heart tissue contracted weakly. Adding a healthyTAZgene normalized these features, suggesting that gene replacement therapy could be a viable treatment.

But to fully capture Barth syndrome and its whole-body effects, Pu and colleagues needed an animal model. The animal model was a hurdle in the field for a long time, says Pu, director of Basic and Translational Cardiovascular Research at Boston Childrens and a member of the Harvard Stem Cell Institute. Efforts to make a mouse model using traditional methods had been unsuccessful.

As described in the journalCirculation Research, most mice with the whole-bodyTAZdeletion died before birth, apparently because of skeletal muscle weakness. But some survived, and these mice developed progressive cardiomyopathy, in which the heart muscle enlarges and loses pumping capacity. Their hearts also showed scarring, and, similar to human patients with dilatedcardiomyopathy, the hearts left ventricle was dilated and thin-walled.

Mice lackingTAZjust in their cardiac tissue, which all survived to birth, showed the same features. Electron microscopy showed heart muscle tissue to be poorly organized, as were the mitochondria within the cells.

Pu, Wang, and colleagues then used gene therapy to replaceTAZ, injecting an engineered virus under the skin (in newborn mice) or intravenously (in older mice). Treated mice with whole-bodyTAZdeletions were able to survive to adulthood.TAZgene therapy also prevented cardiac dysfunction and scarring when given to newborn mice, and reversed established cardiac dysfunction in older mice whether the mice had whole-body or heart-onlyTAZdeletions.

Thats where the challenge will lie in translating the results to humans. Simply scaling up the dose of gene therapy wont work: In large animals like us, large doses risk a dangerous inflammatory immune response. Giving multiple doses of gene therapy wont work either.

The problem is that neutralizing antibodies to the virus develop after the first dose, says Pu. Getting enough of the muscle cells corrected in humans may be a challenge.

Another challenge is maintaining populations of gene-corrected cells. While levels of the correctedTAZgene remained fairly stable in the hearts of the treated mice, they gradually declined in skeletal muscles.

The biggest takeaway was that the gene therapy was highly effective, says Pu. We have some things to think about to maximize the percentage of muscle cell transduction, and to make sure the gene therapy is durable, particularly in skeletal muscle."

Reference: Wang et al. (2020).AAV Gene Therapy Prevents and Reverses Heart Failure in A Murine Knockout Model of Barth Syndrome.Circulation Research.https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.119.315956.

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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Gene Therapy Reverses Heart Failure in Mouse Model - Technology Networks

Skin Stem Cells Comments Off on Gene Therapy Reverses Heart Failure in Mouse Model – Technology Networks | March 13th, 2020

Boston Children's Hospital researchers used an investigational gene therapy to treat heart failure in a mouse model of Barth syndrome. Barth syndrome is a rare genetic disorder in boys that results in life-threatening heart failure. It also causes weakness of the skeletal muscles and the immune system. The disease is caused by a mutation of a gene known as tafazzin or TAZ.

In 2014, William Pu and researchers at Boston Childrens Hospital collaborated with the Wyss Institute to develop a beating heart on a chip model of Barth syndrome. It used heart-muscle cells with the TAZ mutation that came from patients own skin cells. This was able to prove that TAZ was the cause of the cardiac problems. The heart muscle cells did not organize normally and the mitochondria, the cells energy engines, were disorganized, resulting in the heart muscle contracting weakly. By adding healthy TAZ genes, the cells behaved more normally.

The next step was an animal model. The results of the research were published in the journal Circulation Research.

The animal model was a hurdle in the field for a long time, Pu said. Pu is director of Basic and Translational Cardiovascular Research at Boston Childrens and a member of the Harvard Stem Cell Institute. Efforts to make a mouse model using traditional methods had been unsuccessful.

Douglas Strathdees research team at the Beatson Institute for Cancer Research in the UK recently developed animal models of Barth syndrome. Pu, research fellow Suya Wang, and colleagues characterized the knockout mice into two types. One had the TAZ gene deleted throughout the body; the other had the TAZ gene deleted just in the heart.

Most of the mice that had TAZ deleted throughout their whole bodies died before birth, likely from skeletal muscle weakness. Of those that survived, they developed progressive cardiomyopathy, where the heart muscle enlarges and is less able to pump blood. The heart also showed signs of scarring similar to humans with dilated cardiomyopathy, where the hearts left ventricle is dilated and thin-walled.

The mice that lacked TAZ only in their heart tissue that survived to birth had the same features. Electron microscopy indicated that the heart muscle cells and mitochondria were poorly organized.

Pu and Wang and their team then used gene therapy to replace TAZ in the newborn mice and in older mice, using slightly different techniques. In the newborn mice the engineered virus was injected under the skin; in the older mice it was injected intravenously. The mice who had no TAZ in their bodies and received the gene therapy survived to adulthood.

In the newborn mice receiving the gene therapy, the therapy prevented cardiac dysfunction and scarring. In the older mice receiving the therapy, it reversed the cardiac dysfunction.

The study also showed that TAZ gene therapy offered durable treatment of the cardiomyocytes and skeletal muscle cells, but only when at least 70% of the heart muscle cells had taken up the gene via the therapy. Which the researchers point out that when the therapy is developed for humans, that will be the most challenging problem. You cant just scale up the dose because of inflammatory immune responses, and multiple doses wont work either because the body develops an immune response. Maintaining the gene-corrected cell is also a problem. In the heart muscles of the treated mice, the corrected TAZ gene stayed relatively stable, but slowly dropped in skeletal muscles.

The biggest takeaway was that the gene therapy was highly effective, Pu said. We have some things to think about to maximize the percentage of muscle cell transduction, and to make sure the gene therapy is durable, particularly in skeletal muscle.

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Gene Therapy Reverses Heart Failure in Animal Model of Barth Syndrome - BioSpace

Skin Stem Cells Comments Off on Gene Therapy Reverses Heart Failure in Animal Model of Barth Syndrome – BioSpace | March 13th, 2020