Category Archives: Minnesota Stem Cells

Twenty years ago, cardiologist and stem-cell scientist Piero Anversa published an exciting paper. He was then a prominent researcher at New York Medical College in Valhalla, and his data in mice showed that injured hearts could regenerate with the help of stem cells taken from bone marrow1contrary to prevailing wisdom.

Myocardial infarction, commonly known as a heart attack, deprives cardiac muscle cells of oxygen, causing them to perish. The human heart responds by laying scar tissue over lost muscle. But these reconstituted areas dont pump blood as competently as before. In time, this can lead to heart failureparticularly if other heart attacks follow. The implications of Anversas work were clear: stem cells, through their growth and proliferation, had the potential to reverse the damage caused by heart attacks and thereby prevent heart failure.

But other researchers who attempted to replicate these mouse studies found themselves coming up short. Allegations of faked results eventually began to surface, and Anversa, who had since joined Harvard Medical School, and Brigham and Womens Hospital in Boston, Massachusetts, was forced to leave his posts in 2015. Two years later, Brigham and Womens Hospital paid the US government US$10 million to settle allegations that Anversa and his colleagues had used fraudulent data to apply for federal funding. And a 2018 investigation conducted by Harvard called for 31 of Anversas papers to be retracted.

This saga has dampened the enthusiasm that once surrounded research into stem-cell therapy, says Michael Schneider, a research cardiologist at Imperial College London. The controversy, overt scientific misconduct and evidence against Anversas claims has cast aspersions on the field more generally, he admits. Thats unfortunate, because many other stem-cell scientists are conducting legitimate research.

Meanwhile, another heart-healing strategy has emerged, drawing inspiration from species that, unlike humans, can regrow cardiac muscle after trauma. Researchers are seeking to learn more about the molecules produced by zebrafish (Danio rerio) hearts as they heal themselvesand are investigating whether injectable drugs containing the same substances could also yield reparative results.

The question is now whether it will be stem cells, small-molecule drugs or a combination of the two that achieve the goal of convincing the heart to heal instead of scar.

In the wake of the Anversa scandal, there has been an important evolution of thinking on the stem-cells front. A 2019 literature review pointed out that newer studies tend to show the most significant impact from stem-cell therapy comes from the substances the cells secrete, rather than their proliferation2. After many years of work, we find that when we deliver cells into the heart, the benefit of replaced damaged cells is only minor, says the reviews author Javaria Tehzeeb, an internal-medicine specialist at the Albany Medical Center in New York. The real work of regeneration happens, she explains, when the cells produce growth factors, which in turn affect heart repair by reducing inflammation and stimulating the development of new heart muscle.

That means stem-cell therapies share some similarities with the drug strategyessentially it comes down to molecules secreted by the stem cells versus molecules that are directly injected. But they also have important differences.

First, part of the stem-cell therapy benefits might still come from the cells proliferation, even if that bonus is relatively small. Second, theres little control over what substances the stem cells produce once theyre injected, whereas specific molecules can be administered at known doses. And finally, the logistics of scaling up and delivering these two therapies will be very different.

A study published in 2020 showcased the importance of stem-cell-produced molecules by looking at the structural integrity of proteins found in infarcted mouse hearts3. The scientists artificially induced heart attacks in eight adult mice. Four weeks later, they administered stem cells to half the rodents. After a further four weeks, their hearts were removed and washed with a series of buffer solutions and chemical reagents to extract the proteins, which were then analysed. We essentially did a massive scan of every single protein in the heart, says Andre Terzic, lead author of the study. The authors were able to identify almost 4,000 proteins, and showed that heart attacks distorted the structure of 450 of them. But with stem-cell therapy, that number fell to 283.

Proteins are the intimate components that make our hearts work properly, and when the heart is diseased, they become damaged, says Terzic, who is director of the Mayo Clinic Center for Regenerative Medicine in Rochester, Minnesota. The ability of these stem cells to secrete healing signals is probably a key element to what weve observed.

All cells and tissues are constantly telling each other what they need and whether theyre stressed through molecular signalling. When you lose a chunk of cells in a heart attack, you lose part of that conversation, explains Charles Murry, an experimental pathologist and director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington in Seattle. Injected stem cells could be filling in the missing dialogue by secreting signalling and rescue molecules, he explains.

Although this sounds encouraging, there are still parts of the stem-cell-therapy approach that need to be finessed. In a 2018 study, Murry and colleagues transplanted approximately 750 million cardiomyocytes into macaque monkeys that had experienced major heart attacks4. One month after the intervention, the amount of blood pumped by their hearts had increased by 10.6% compared with just 2.5% in the control group. This advantage persisted three months later, but one out of the five stem-cell-treated monkeys suffered arrhythmias. The onset of arrhythmia wasnt previously observed in small-animal studies, but it is a known complication of heart attacks. Nevertheless, the researchers thought it could be a potential side effect of the stem-cell infusion. Obviously it isnt statistically significant, but common sense led us to classify this as a treatment complication, says Murry.

In addition to safety concerns, stem-cell therapies are also beset by questions of practicality. Think of a lab with all these cell culture flasks where you have to grow millions of cells just to create a single dose, says Terzic. Now imagine tens of thousands of patients. Its a formidable effort to be ready, especially if you want to intervene rapidly. You dont have the luxury of time to build up supplies.

Thats one reason why some people think the promise of cardiac rejuvenation lies elsewhere. Theres been an awful lot of time and money spent on stem-cell therapy, raising false hope in patientsand so far, the clinical outcomes have been largely disappointing, says Paul Riley, a cardiovascular scientist at the University of Oxford, UK. Riley is investigating whether inserting specific molecules into the heart might be more effective.

Human hearts cant regenerate on their own, but other animals do have such abilities. Zebrafish, for example, can regrow their hearts after as much as 20% is removed. Newborn mice can also regenerate heart tissue. Observing the molecular pathways in these animals might make similar results possible in humans.

Research has shown that following a myocardial infarction in zebrafish, the epicardiuma membrane surrounding the heart muscleproduces molecular signals that might kick-start muscle-cell regeneration5. The hope is that manipulating the human epicardium could elicit the same therapeutic results. There are probably approaches we can take to target the cells that exist in the heart with small molecules or drugs, that could invoke repair and regeneration, says Riley.

Back in 2011, Riley and colleagues showed that this is theoretically possible6. They pre-treated adult mice with a daily injection of a protein called thymosin 4 for one week before inducing an infarction, and found that these mice were able to produce new cardiac muscle. This offers a road map to a pre-emptive therapy. If an individual is at high risk of a heart attack, says Riley, then its conceivable they could be advised to take a priming or preventative therapeutic, which may counteract an event, but its not quite the holy grail of restoring lost tissue after a heart attack that were searching for. In other studies, Riley has since shown that other proteins besides thymosin 4 might also have a role in stimulating the epicardium to regenerate the heart7.

Its easier to see how the drug route offers clearer prospects for scaling upbut the science behind this approach is newer, and there havent been any clinical trials in humans yet. What goes in stem cells favour is the body of work behind them, says Tehzeeb.

It might be that stem-cell therapies achieve government approvals first, but then drugs overtake them once the science and research have had time to catch up. When we get to the end of the line with molecules, then maybe we can say stem cells are a thing of the past, Tehzeeb says. But until then, we should continue to pursue their potential.

Murry echoes that sentiment, arguing that findings from both camps could end up helping everyones research. We need an ecosystem with a competition of ideas, and as long as its all openly published then well figure it out, he says. Thats the better approach, rather than saying my idea is better than your idea.

This article is part ofNature Outlook: Heart health, an editorially independent supplement produced with the financial support of third parties.About this content.

Orlic, D.et al.Nature410, 701705 (2001).

Tehzeeb, J., Manzoor, A. & Ahmed, M. M.Cureus11, e5959 (2019).

Arrell, D. K., Rosenow, C. S., Yamada, S., Behfar, A. & Terzic, A.npj Regen. Med.5, 5 (2020).

Liu, Y.-W.et al.Nature Biotechnol.36, 597605 (2018).

Cao, J. & Poss, K. D.Nature Rev. Cardiol.15, 631647 (2018).

Smart, N.et al.Nature474, 640644 (2011).

McManus, S.et al.J. Mol. Cell. Cardiol.140, 3031 (2020).

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Cells or drugs? The race to regenerate the heart - Scientific American

Celia Grace traveled from Alabama to Minnesota for the procedure but her new stem cells traveled all the way from Italy.

A 4-year-old girl with a rare, life-threatening disease, has become the first patient to receive a cutting edge gene therapy treatment in the U.S.

Two weeks ago, Celia Grace Hamlett traveled from her home in Alabama to Minnesota, in order to receive an infusion of stem cells that traveled all the way from Milan, Italy. But just before the groundbreaking procedure was scheduled to begin, her insurance threatened to pull the plug.

Her insurance reversed its decision to deny coverage hours after a KARE11 report on the treatment. The uncertainty delayed the procedure by several days.

Celia Grace has a rare disease called metachromatic leukodystrophy (MLD), in which her body can't produce an enzyme that protects the brain and nervous system. If left untreated, MLD is often fatal just a few years after symptoms begin. Fortunately, Celia grace is still asymptomatic, which is why she was the perfect candidate to make medical history in the US.

This summer, Celia Grace traveled to Minnesota so that her stem cells could be removed and sent to Italy to get re-engineered. For several years, a gene therapy trial in Milan has helped many patients stop the progression of MLD, but it took the University of Minnesota Medical School several years to get the FDA to approve the treatment in the US.

On Monday, Celia Grace finally received the long-awaited infusion of her re-engineered cells. So far, she has not suffered any complications.

"It was just a great feeling. It was just unreal that it was here and then, now, it's done," said Kassie Hamlett, Celia Grace's mom. "We were all joking around saying, 'We've waited this long, it's like there should be a drumroll or something. It was very good, she handled it very well and, you know, she's just suffering from boredom right now. It's kind of hard to keep a four year old in the same place for several hours."

Don't be fooled by her boredom, Celia Grace has been through a lot. She had to undergo several days of chemotherapy before she could get the infusion. Her doctors say she'll remain in the hospital for several weeks as her new cells grow. After that, they'll follow her closely because of what this treatment could mean for so many others.

"The goal of the procedure is to give her a normal, healthy life, so we'll be following her for at least 15 years, following the procedure, to make sure that things are going well," said Dr. Paul Orchard, a Pediatric Blood and Marrow Transplant Physician at M Health Fairview. "The technology that we're using for Celia can be applied to a number of different types of disorders. Some of them are enzyme difficiencies like hers, some are red blood cell problems like sickle cell anemia, so there is great utility in these new approaches. This is where the field is going."

Read more:
Four-year-old with rare disease finally gets historic gene therapy treatment - KARE11.com

BERKELEY, Calif., Sept. 29, 2021 (GLOBE NEWSWIRE) -- Caribou Biosciences, Inc. (Nasdaq:CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, announced today it has appointed Ran Zheng to its board of directors. Ms. Zheng brings over 25 years of biotechnology industry leadership experience in biologics drug development with broad expertise in technical operations and the manufacture of gene and cell therapies.

It is my pleasure to welcome Ran to our board of directors,” said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. Ran brings a wealth of strategic and operational expertise in the development of gene and cell therapies, from engineering and process development through manufacturing and supply chain management. We look forward to benefitting from her perspective and experience as we advance our chRDNA-edited allogeneic CAR-T and CAR-NK cell therapies for the potential treatment of challenging hematologic malignancies and solid tumors.”

Caribou has developed an innovative and differentiated genome-editing technology that enables a pipeline of off-the-shelf allogeneic cell therapies designed to increase persistence and anti-tumor activity,” said Ms. Zheng. The work Caribou is doing to develop allogeneic cell therapies has the potential to make a real difference in the lives of patients with serious diseases. Caribou is clearly a leader in this field, and I am excited to join its board of directors.”

Ms. Zheng currently serves as chief executive officer and on the board of directors of Landmark Bio, a public benefit limited liability company that was formed to advance the development of transformative new medicines by translating today’s cutting-edge research into tomorrow’s breakthrough therapies. Landmark Bio focuses on the emerging technologies of cell and gene therapies, mRNA, and other novel modalities to enable and accelerate drug development and biomedical innovation. Prior to joining Landmark Bio earlier this year, Ms. Zheng most recently served as chief technical officer at Orchard Therapeutics, a commercial-stage global gene therapy company specializing in hematopoietic stem cell-based gene therapies. In that role, Ms. Zheng led the technical operations organization and helped advance the company’s product pipeline, including contributing to the approval of Libmeldy® therapy in Europe, the first gene therapy product for metachromatic leukodystrophy. Ms. Zheng has also held leadership positions at multiple biotechnology companies including Genzyme (now Sanofi) and Amgen. At Amgen, Ms. Zheng held positions of increasing responsibility in process development, clinical and commercial manufacturing, as well as supply chain, and played a key role in building differentiated capabilities in manufacturing for clinical supply and commercial product launch to enable speed to clinic and speed to market strategies for Amgen’s innovative products. Ms. Zheng received an M.S. in microbial engineering from the University of Minnesota and a B.S. in biology from Beijing Forestry University.

About Caribou’s Novel Next-Generation CRISPR Platform CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Type II CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems occasionally edit unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed chRDNAs (pronounced chardonnays”), RNA-DNA hybrid guides that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of the chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

About Caribou Biosciences, Inc. Caribou is a clinical-stage CRISPR genome-editing biopharmaceutical company dedicated to transforming the lives of patients with devastating diseases by applying the company’s proprietary chRDNA technology toward the development of next-generation, genome-edited cell therapies. The company is developing a pipeline of genome-edited, off-the-shelf CAR-T and CAR-NK cell therapies for the treatment of both hematologic malignancies and solid tumors against cell surface targets for which autologous CAR-T cell therapeutics have previously demonstrated clinical proof of concept, as well as additional emerging targets.

Forward-Looking Statements This press release contains forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements related to Caribou’s pipeline of cell therapies, potential treatments, and expectations regarding its business. Management believes that these forward-looking statements are reasonable as and when made. However, such forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from any future results expressed or implied by the forward-looking statements. Risks and uncertainties include without limitation the risks inherent in drug development such as those associated with the initiation, cost, timing, progress and results of current and future research and development programs, preclinical and clinical trials, as well as other risk factors described from time to time in Caribou’s filings with the Securities and Exchange Commission, including its final prospectus filed on July 23, 2021. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, Caribou undertakes no obligation to update publicly any forward-looking statements for any reason.

For more information about Caribou, visit http://www.cariboubio.com and follow the company @CaribouBio.

Caribou Biosciences” and the Caribou logo are registered trademarks of Caribou Biosciences, Inc.

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Caribou Biosciences Appoints Biotechnology Industry Veteran Ran Zheng to its Board of Directors - Stockhouse

Aug. 14Post Bulletin reporter Nora Eckert's ongoing series of stories on organ transplants have been shining a light on a critical need in Minnesota and the U.S.

More than 100,000 men, women and children are on the national transplant waiting list, every nine minutes or so another one is added, and on average 17 people die each day waiting for an organ transplant.

Eckert has told us about Ken Hanson, our former work colleague at the Post Bulletin, who waits for a kidney transplant as he is supported by a team of friends and caregivers.

And we have read about Linda and Tom Christopherson, a husband and wife whose transplant story, about the heart-shaped kidney Linda gave to Tom, touched our hearts.

In Rochester, more than 1,000 people wait for a viable organ donor to be found to help them. If you find it in your heart or your kidney, or pancreas to be a donor to help them, here are some things to know. These facts come from the website of the Health Resources and Services Administration, organdonor.gov.

You have to be 18 or older to make yourself a donor, and there's no strict upper age limit, although donors have to be in generally good health to be accepted. Donors under age 18 can do so with permission of a parent or guardian.

Eight vital organs heart, kidneys, pancreas, lungs, liver, intestines, hands, and face can be donated, as can tissue (including corneas), bone marrow and stem cells.

Race is not a factor in matching donors and recipients, but minorities have a higher need for transplants, because some diseases that cause end-stage organ failure are more common in these groups of people.

Having an organ donor card or checking the organ donor box on your driver's license may not be enough to guarantee your organs will be donated. It's necessary to enroll in your state registry, a process that is described at organdonor.gov. It's also a good idea to talk to your family about your intent to donate.

Story continues

If you want to donate your body for scientific research not an uncommon desire in the Med City you might not be able to also donate specific organs. Consult your medical provider to see what may be permitted.

Blood donations also are sorely needed at this time.

You've heard the saying about wealth, "You can't take it with you." Same goes for our body parts that might be used to prolong others' lives. Consider being a donor.

Read more:
EDITORIAL: The need is vast. Consider becoming an organ donor. - Yahoo News

Post Bulletin reporter Nora Eckerts ongoing series of stories on organ transplants have been shining a light on a critical need in Minnesota and the U.S.

More than 100,000 men, women and children are on the national transplant waiting list, every nine minutes or so another one is added, and on average 17 people die each day waiting for an organ transplant.

Eckert has told us about Ken Hanson, our former work colleague at the Post Bulletin, who waits for a kidney transplant as he is supported by a team of friends and caregivers.

And we have read about Linda and Tom Christopherson, a husband and wife whose transplant story, about the heart-shaped kidney Linda gave to Tom, touched our hearts.

In Rochester, more than 1,000 people wait for a viable organ donor to be found to help them. If you find it in your heart -- or your kidney, or pancreas -- to be a donor to help them, here are some things to know. These facts come from the website of the Health Resources and Services Administration, organdonor.gov.

You have to be 18 or older to make yourself a donor, and theres no strict upper age limit, although donors have to be in generally good health to be accepted. Donors under age 18 can do so with permission of a parent or guardian.

Eight vital organs -- heart, kidneys, pancreas, lungs, liver, intestines, hands, and face -- can be donated, as can tissue (including corneas), bone marrow and stem cells.

Race is not a factor in matching donors and recipients, but minorities have a higher need for transplants, because some diseases that cause end-stage organ failure are more common in these groups of people.

Having an organ donor card or checking the organ donor box on your drivers license may not be enough to guarantee your organs will be donated. Its necessary to enroll in your state registry, a process that is described at organdonor.gov. Its also a good idea to talk to your family about your intent to donate.

If you want to donate your body for scientific research -- not an uncommon desire in the Med City -- you might not be able to also donate specific organs. Consult your medical provider to see what may be permitted.

Blood donations also are sorely needed at this time.

Youve heard the saying about wealth, You cant take it with you. Same goes for our body parts that might be used to prolong others lives. Consider being a donor.

Read more here:
Our View: The need is vast. Consider becoming an organ donor. - PostBulletin.com

What started out as a journey to better understand regulatory T cells has now led to an intriguing approach with an investigational cell therapy designed to prevent the risk of graft-versus-host disease (GVHD) and to improve relapse-free survival rates in patients undergoing hematopoietic stem cell transplantation (HSCT).

Data of a phase 1/2 trial recently showed that the first-generation precision cell treatment Orca-T compared with a historical control of standard HSCT demonstrated faster neutrophil (median, 12 days vs 14 days; P < .0001) and platelet engraftment (median, 11 days vs 17 days; P < .0001), decreased incidence of grade 2 or higher GVHD at 100 days (10% vs 30%, P = .005) and chronic GVHD at 1 year (3% vs 46%, P = .0002).1,2

The 1-year GVHD-free and GVHD relapse-free survival (GRFS) rates were 75% with the use of Orca-T vs 31% with standard HSCT (P < .0001). The comparator cohort was derived from contemporaneous patients who had been treated at Stanford University with a conventional allograft.

Along with feasibility of the approach, the results also highlight how Orca-T demonstrates potent anti-leukemic activity in patients who have active disease at HSCT, which suggests that the decrease of GVHD does not impact graft-vs-leukemia (GvL).

That is the most exciting part about the Orca-T story; it is the ability to do this with precision, with speed, and to export it to other sites. The results are intriguing, and very supportive, said Robert Negrin, a professor of medicine (blood and marrow transplantation), and chief of the Division of Blood and Marrow Transplantation at Stanford University.

In an interview with OncLive, Negrin, who is senior author on the trial, shared the evolution of Orca-T as a novel approach to HSCT, highlighted his robust experience with using this cell therapy at Stanford University, and how Orca-T is a potential prevention method for GVHD.

OncLive: Please provide some background to this therapeutic approach. What is the mechanism of action? How is it effective in patients undergoing transplant?

Negrin: This whole idea came from mouse studies many, many years ago, where we identified GVHD as being a dysregulated immune reaction that just keeps going, and going, and going. Like you and I, when we react to something, we have a reactionlet's say, influenza. Our body responds, and then we stop reacting and you get better. With GVHD, what we noticed in using a bioluminescent animal model is that the alloreactive T cells just keep going, going, and going and are unrelenting in mice, just like in people. The problem is very similar and affects certain organs in a very similar way.

Therefore, we went about trying to understand the use of so-called regulatory cells. These are cells that everybody has that help control immune reactions. We just applied them in this clinical scenario, first in mice work done by Matthias Edinger, MD, when he was a postdoctoral fellow many years ago [and other researchers]. All of them were very actively involved in these studies, and showed, somewhat surprisingly, that the administration of regulatory T cells could control this dysregulated immune response that we called GVHD.

Probably more surprising was that, at least in the animal models, it also allowed for the benefits of transplant, namely, the graft-vs-tumor effect and better immune recovery. This was in large part because GVHD also impacts the immune repertoire and where the immunity is developed in the recipient.

All of this was very nice in mouse models and was very elegant. We did a lot of studies, published a number of nice papers, and thought this would be a great idea because it sort of solved, or at least addressed, the principal problems after bone marrow transplantationnamely, avoidance of GVHD yet retention of graft-versus-tumor effects and better immunity. A lot of times, people say, "Oh, that sounds good in mice, but, that's too good to be true." And, theyll ask, "Will that all work in people?"

Where did the biggest challenges lie in this approach?

The big challenge came about to try to apply this to patients. We also have one other interesting point that is relevant. If we gave the regulatory T cells first, before the so-called conventional CD4+/CD8+ cells, that allowed for a lower dose of regulatory T cells. This is because a big challenge is the paucity of these cells; you and I don't have that many.

Then, the other big challenge was the technical ability to isolate in cells. What we do in mice is cell sorting, which is a standard technology. But, that was not developed in people because we're bigthere are a lot of cells, and cell sorting is rather slow, and it's very specific. To get enough cells takes a really long time. It's somewhat of a heroic thing to do in people, to get the adequate amount ourselves; of course, we don't really know what this proper cell dose is.

However, what we thought we learned was that the ratio of conventional to regulatory T cells was the key component. Also, if you give the regulatory T cells first, you can get fewer numbers. Those are things you can do in transplant. You can get the cell from the donor, and you can give cells in a certain sequence; all of those things are very doable. It seemed like an attractive thing to do in patients.

Then, the question was: Does it work? There are 3 groups that have really pioneered this work. The first study came from the University of Perugia in Italy. They did this in haploidentical transplantation; you cannot avoid immunosuppression in haploidentical transplants. They were able to show in several nice papers that you could do this strategy, and seemingly, get away with low risk of GVHD, and also low relapse. This is because the other issue is: how do you measure the graft-vs-tumor effect? There is no assay, and we have no test; you have to wait and see who relapses and who doesn't. Therefore, they also showed rather convincingly that you could reduce GVHD risk, yet, there was a very low risk of relapse in their high-risk patient population. Those were very important [data].

Another study from the University of Minnesota did this with umbilical cord blood. They expanded the regulatory T cells from a third cord blood unit, which is somewhat heroicit is another level of complexity to isolate the cells and then expand them. We did this in matched donorseither matched siblings or matched unrelated donors. We published a paper in JCI Insight several years ago showing the initial results, and they look quite favorable.

Therefore, what I think is most exciting about what Orca Bio has done is they are developing technology to isolate the cells more quickly, to be able to do this on a clinical scale, with precision, and with speed. Also, [they are developing the technology] to be able to distribute it to anybody, because the criticism of all these studies is that, "Oh, that's nice. But, this is a single-institution study. Is this really true? Can this be exported? Could this be something that [an organization] other than these [individual] centers are really focused in this area and have developed these technologies could really do? Orca Bio is developing the technology, and improving the technology, because it's still very cumbersome, and exporting the technology so that you could do this, theoretically, at any center.

That's what I think is most exciting about the Orca Bio abstract; it is demonstrating that this can be done. It certainly opens the door to prevention of GVHD. As we move into an era of using cell-based therapeutics, now, this opens up many other possibilities, because you use these regulatory cells and autoimmune disorders and organ transplant tolerance. There are many other cell types that have potential clinical utility, but getting them, and purifying them, is a big challenge. There are many other possibilities that one could think of.

Obviously, more time will be required to follow these patients, but they certainly are supportive of the idea that you can improve overall outcomes using this strategy. That's what we hope to be able to demonstrate further.

Please focus on the scalability of this approach. Through these types of collaborations, how do you see Orca-T potentially moving through the FDA pipeline?

In academia, we don't develop drugs. It's too much, we don't have the resources, we don't have the capability, and we don't have the monitoring capability that is required for multi-institutional studies. Where these commercial partners come in is, they can raise money for interesting concepts, which Orca Bio has done, and they can export this to other centers, and that's critically important.

As we've seen in the CAR T-cell [therapy] world, that can be a quite successful commercial business. Also going through the process of an FDA approvalwhich Orca Bio is moving along in that processand getting the right designations is critically important to commercial entities. In academia, it's important to us, but that's just not our focus.

We don't have the resources around, the people and the expertise to really drive things through that process. We're good at developing the studies and getting FDA approvals, and [investigational new drug applications], but not really [good at] developing drugs as a commercial entity. This collaboration is key to doing this successfully; for example, at Orca Bio, [they have] technology to separate cells more efficiently and effectively. They also have the resources to do a multi-institutional clinical trial, and the expertise to move something through and present it to the FDA. Those are key components.

Could you expand on the study and respective data from this phase 1/2 trial?

Here at Stanford Cancer Institute, we did find in our patients that giving low doses of immunosuppressive medications with a single agent seem to improve the outcomes, and it's remarkable how well these patients have gone through the transplant. It's a little bit hard to appreciate an abstract until you take care of these patients, and many of them just sort of move to the transplant with relatively little challenges. We have not seen greater risks of things like infection [or] disease recurrence; those are obviously things that will be followed.

When we look at the 1-year GVHD relapse-free survival rate, which is an endpoint that most transplant studies would agree is the most important end point, the overall outcomes are much more favorable compared with a historical control group.

The data are very encouraging, and the overall outcomes look very strong in a reasonable number of patients now. We think it's important for the community to hear about it, and to get it on everybody's radar, and be excited about trying to move this forward as a more standard therapy. This is still a clinical trial, so it's not, it's not part of any standard therapies yet. We are using this quite regularly and have been very encouraged by the ease of which patients go through the transplant. It's still an allogeneic transplant; there still are many challenges there. However, these patients seem to be doing quite well, we're very encouraged, and so we keep going.

How does this approach impact patient outcomes as it relates to quality of life (QoL)?

The hard end points of 1-year relapse-free survival is obviously the most important to patients. However, going through an allogeneic transplant is obviously an incredibly difficult thing. Fortunately, I've only seen it [from] the doctor side, not [as a] patient.

However, I've seen many, many patients, and the quality of their life as they go through this experience is very important to all of us. As we saw these patients go through these studies, we felt like we were capturing something that was really important, and that is the ease [at which] many patients went through this experience, which just seemed different. It's hard to capture that.

It's really important for patients to speak and, and the way patients speak is in different ways. One way is through the QoL measures that they answer. This is [what they find] important, this is what they experiencednot what we say is happening. That's really important to hear that voice too. Those are data we're trying to collect. It's not so easy, because going through a bone marrow transplant is a poor QoL for everybody. But, by just to trying to capture this, [Orca-T seems] better than what we what we thought.

How has this changed the mindset of cell-based approaches in the community?

What has changed is the belief in the concept of cell-based therapies. A lot of these things are somewhat fanciful. It is also important to show that we can translate from an animal model [to a human]. There is a lot of criticism of animal modeling, because people say, "Well, it's nice for animal models, but it doesn't really translate into the clinic." Actually, my view is that because we don't actually follow the animal models, there are many compromises one needs to make. When you translate studies from animals to humans, there are many differences, and it's really important to try to follow them as carefully as you can within the limitations of what is possible. We were very engaged in that and tried to follow as carefully as we could. To me, that is very encouragingthat you can study things in animals that generate new concepts and be able to translate that into a clinical trial.

Obviously, with all of the caveats of an early-phase clinical trial, more time needs to pass, more patients to be treated, and you need to export [the treatment] to other centers. That's a really important point, because there are many things that get lost because, "it's too complicated. It's too expensive. People can't do it." I don't think anybody can do high-speed cell sorting, as a clinical project in a standard or standard cell-processing laboratory. It's above the level of what most processing laboratories can do.

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Negrin Shines Light on the Orca-T Story in GVHD - OncLive

Karen Wils photoShown at right is Karen Wils, the Chemo Beagler or the COVID Beagler.

ESCANABA The year 2020 has put me and most everybody else in a very unusual position.

We all feel a little trapped and uneasy thrown into a situation we have never faced before.

I always kind of thought I would need to have a stem cell transplant someday after I was diagnosed with multiple myeloma in 2008.

I often referred to this blood cancer as my pesky woodtick. Fortunately, I have been blessed with good control of the disease until this year.

Leaving home, going to the Mayo Clinic and going through transplant is enough excitement for one person, but to be doing that while COVID-19 plagues our country is almost too much.

To say the last few months have been an interesting journey would be putting it mildly.

As the summer drew to a close, many changes were closing in on me, too. My son went off to a new job, and my daughter left for college. The very next week, my husband and I left for Minnesota for an unknown amount of weeks for my stem cell transplant.

For three-and-a-half weeks we were at Mayo. My husband was my excellent care giver through the strong chemo, and the transplant of my own stem cells and the long road to recovery.

Doing all of this during a pandemic is really interesting. The Mayo Clinic takes COVID-19 very seriously. So with much testing, temperature taking, sanitizing and constant mask wearing, we maneuvered through the treatment.

Social distancing when you are staying at the Gift of Life Transplant House and so far from home is very difficult. Phone calls, Zoom and Facebook became my life link to the kids, family and friends.

After going through some pretty weak days, finally my new immune system was strong enough for me to go home.

Oh, the great joy of heading down those last miles from Menominee to Escanaba back into the land of trees and water!

Sleeping in my own bed, seeing my pets, and being able to stand in my own garden felt so wonderful, but the house was so quiet without the kids.

The COVID-19 cautions had to continue, too.

I wear my mask and feel a little bit trapped, like everybody else these days. I pray that I am making all healthy decisions when I encourage my children to go to church or my husband to go to the grocery store.

The COVID-19 virus threatens big things and little things like family traditions that have to be rethought. With great sadness, I postponed until next year our annual camp gathering/harvest festival. So many folks have been through canceled or postponed parties, birthdays, anniversaries and funerals.

As hard and as disappointing as this is, the important things remain. The trees still are changing to awesome autumn colors. The harvest season is in full swing. The wild animals are still thriving outside our windows, and our families are together even if we cant do everything we want to do right now.

As I get stronger every day, I thank God. I pray for a cure for COVID-19. Yoopers are tough and our traditions will thrive long after this pandemic!

Karen (Rose) Wils is a lifelong north Escanaba resident. Her folksy columns appear weekly in Lifestyles.

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COVID-19 and the trials of treatment | News, Sports, Jobs - Escanaba Daily Press

MINNEAPOLIS, Oct. 6, 2020 /PRNewswire/ --The National Marrow Donor Program (NMDP)/Be The Match today announced a collaboration with the Minnesota health system M Health Fairview and Marcus Center for Cellular Cures (MC3)/Carolinas Cord Blood Bank at Duke University (Duke) to offer cryopreservation services to transplant centers through the Be The Match BioBank. The collaboration brings together industry-leading expertise in cryopreservation and storage of patient-directed donor blood stem cell products to improve donor availability, collection quality, and ultimately, to provide a more reliable path to transplant for patients.

Through the Be The Match BioBank, blood stem cell donors will be able to donate bone marrow or peripheral blood stem cells (PBSC) for an intended patient on a timeline that is convenient for the donor. The cells are then cryopreserved and stored for the transplant center at no cost to them and shipped to coincide with initiation of the patient's conditioning regimen and optimal treatment timeline.

"We're excited to expand our partnership with Duke University by adding the expertise of physicians and researchers at M Health Fairview University of Minnesota Medical Center to continue to overcome logistical barriers to blood and marrow transplantation that might otherwise disrupt optimal patient care. Through the flexibility offered by the Be The Match BioBank, we believe we can provide transplant centers with a well-matched, available donor more often, and allow the transplant to occur at the best time for the patient," explained Steven Devine, MD, Chief Medical Officer, NMDP/Be The Match, and Associate Scientific Director, CIBMTR (Center for International Blood and Marrow Transplant Research). "The team at the Duke University lab was instrumental in the development of the Be The Match BioBank, as well as supporting donor product cryopreservation during the COVID-19 pandemic to ensure patients can continue to receive the transplants they need."

"We are proud to extend our partnership with the NMDP/Be The Match in a new way. Be The Match BioBank is an innovative way to remove barriers that otherwise may stand in the way of a patient's transplant," said Joanne Kurtzberg, MD, who leads the Marcus Center for Cellular Cures (MC3)/Carolinas Cord Blood Bank at Duke University.

"We are thrilled to be working with the NMDP/Be The Match to offer Be The Match BioBank. Through this partnership, transplant physicians can have confidence a high-quality bone marrow or PBSC product will be available from the donor they requested in the timeframe that works best for their patient," said David McKenna, MD, who leads the Molecular and Cellular Therapeutics program at M Health Fairview.

Be The Match BioBank can be used by any transplant center in the NMDP/Be The Match Network of more than 180 transplant centers worldwide. Blood stem cell donors are informed that the transplant center is requesting cryopreservation and provide consent prior to collection. Donors can also consent to having their donated cells made available to other searching patients in the unlikely event the intended patient is unable to proceed to transplant as planned.

To learn more about Be The Match BioBank, visit Network.BeTheMatchClinical.org/BioBank.

About the National Marrow Donor Program/Be The Match The National Marrow Donor Program/Be The Match is the global leader in providing a cure to patients with life-threatening blood and marrow cancers like leukemia and lymphoma, as well as other diseases. The organization manages the world's largest registry of potential blood stem cell donors and cord blood units. The NMDP/Be The Match partners with a global network to connect patients to their donor match for a transplant, and provides education and support for patients. Through Be The Match BioTherapies, the NMDP/Be The Match partners with cell and gene therapy companies to support the development and delivery of new therapies. The organization conducts research through its research program, CIBMTR (Center for International Blood and Marrow Transplant Research), in collaboration with Medical College of Wisconsin.

About M Health Fairview M Health Fairview is the newly expanded collaboration betweenthe University of Minnesota, University of Minnesota Physicians,and Fairview Health Services. The healthcare system combines the best of academic and community medicine expanding access to world-class, breakthrough care through its 10 hospitals and 60 clinics.

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NMDP/Be The Match partners with M Health Fairview and Duke University cryopreservation labs to launch Be The Match BioBank - Watauga Democrat

Children of all ages and plenty of adults, too, were simultaneously entertained and educated Saturday at the opening of the Reading Science Center, Berks County's first STEM-themed attraction.

Some attendees designed roller coasters as a lesson about how potential energy and kinetic energy work. Others yanked on ropes tied to bowling balls, a pulley system designed to demonstrate how gears help bicyclists climb hills. And more still spent time their time in the cell lab taking part in experiments such as DNA extraction.

The center features 30 interactive science exhibits, plus educational programs.

"It's for ages 2 to 102," said Reading Science Center founder and board president Jim Cinelli, stressing that the exhibits aren't just fun for children. "I love this stuff."

That being said, part of Cinelli's mission is to expose students to what are often referred to as the STEM disciplines science, technology, engineering and math with the goal of generating interest in those career fields.

"There was one study that shows STEM science centers are effective in doing that," said Cinelli. "Kids will be 30 to 40% more likely to enter a career in STEM if they get to a science center three or more times before seventh grade."

For some families, that's easier said than done.

"That's the kicker: three or more times," said Cinelli. "Your community is at a disadvantage if you don't have one locally."

Cinelli notes that many surrounding areas already have a STEM attraction, rattling off Lancaster, Harrisburg, Allentown and Philadelphia as examples.

However, there was no such place in Berks, a region with 18 school districts.

"We not only wanted it to be in Berks County," said Cinelli, "but for the really underserved population of Reading, we wanted it to be downtown so really it's accessible to everyone."

The Reading Science Center plans to host school-sponsored events and field trips, though those are on hold due to the coronavirus.

Other activities inside the 7,000-square-foot Reading Science Center located inside the multi-use building at 645 Penn St. include a structural engineering where participants can build a bridge and test its stability in an earthquake; a sand pendulum that demonstrates how gravity works; and an early learners section where young children can build on Lego tables.

The cell lab is one of the center's highlights.A donation from the Science Museum of Minnesota valued at about $500,000, it allows visitors to study their own cells under a microscope.

"I don't think you're going to find anything like this anywhere in our area," Cinelli said.

Classroom space is available for workshops, seminars and group experiments.

President of Reading-headquartered Liberty Environmental Inc., Cinelli had been pushing to get the Science Center open for more than three years, describing what he saw as an area of need for the community where he lives.

"I'm here for good," Cinelli said. "I'm born and raised in Berks, have my business here, bought a building downtown three years ago so I have a vested interest in seeing Berks County and the city of Reading thrive."

Cinelli was quick to credit the work by volunteers, some of whom were working right up to opening to ensure all the exhibits were ready.

Mary Chown, interim executive director for the Reading Science Center, assisted in securing donations from individual donors and local foundations to turn a vision into reality.

Donations can be made by visiting readingsciencecenter.org or by emailing Chown at mary.chown@rdgsci.org.

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Berks County's first STEM-themed attraction opens, delights visitors young and old - Reading Eagle

Doctors at the University of Minnesota are the first in the U.S. to treat a critical COVID-19 patient suffering from lung failure using stem cells.

A Food and Drug Administration-approved study will examine a new treatment using mesenchymal stem cells to intervene when a COVID-19 patients immune system becomes overactive and can lead to organ damage and often lung failure. This cytokine storm has been one of the more perplexing and fatal complications of a coronavirus infection.

The inflammation seen in patients with severe COVID-19 can be devastating, Dr. David Ingbar, a critical care and pulmonary physician at the M Health Fairview University of Minnesota Medical Center, said in a statement. The cytokine storm can rapidly lead to shock, massive fluid buildup in the tissues, and direct severe tissue injury, most often in the lungs.

A team of researchers at the university developed the treatment and are leading a study of its effectiveness with other clinicians around the country. Mesenchymal stem cells have been used successfully with other inflammatory conditions including in COVID-19 patients in Italy and China.

Researchers hope the stem cells will slow the cytokine storm and protect lung tissue from damage.

In order to determine the real benefit of MSCs in these very ill patients, patients will be randomized to receive three doses of MSC 48 hours apart or a placebo solution, said John E. Wagner, MD, cancer researcher and director of the Institute for Cell, Gene and Immunotherapy at the University of Minnesota.

The cells being used in this treatment were produced at the universitys molecular and cellular therapeutics center which develops materials such as cells, tissues, antibodies and proteins to be used in clinical trials.

The new treatment being studied at the University of Minnesota was announced as state health officials recorded seven new COVID-19 fatalities on Thursday. Those whose deaths were reported ranged in age from their 40s to their 90s.

The states death toll has reached 1,685 people with another 46 fatalities suspected to have been caused by COVID-19, but the patient did not have a positive coronavirus test.

With 697 new cases announced Thursday, Minnesota now has 62,993 laboratory-confirmed infections with cases in all 87 counties. Most patients are in the Twin Cities metro, but rural counties with meat processing facilities have the most cases per capita.

Health officials reported the results of 15,271 tests Thursday, a marked increase from earlier this week when the number of test results was lower than average.

Minnesota has screened 1.2 million samples from 963,096 patients since local testing started in March. The test positivity rate stands at about 5.3 percent.

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Coronavirus Thursday update: UMN announces new stem cell ...