Category Archives: Minnesota Stem Cells

June 27, 2020

Following promising phase 1 testing, Mayo Clinic is launching phase 2 of a randomized clinical trial of stem cell treatment for patients with severe spinal cord injury. The clinical trial, known as CELLTOP, involves intrathecal injections of autologous adipose-derived stem cells.

"The field of spinal cord injury has seen advances in recent years, but nothing in the way of a significant paradigm shift. We currently rely on supportive care. Our hope is to alter the course of care for these patients in ways that improve their lives," says Mohamad Bydon, M.D., a neurosurgeon at Mayo Clinic in Rochester, Minnesota.

The first participant in the phase 1 trial was a superresponder who, after stem cell therapy, saw significant improvements in the function of his upper and lower extremities.

"Not every patient who receives stem cell treatment is going to be a superresponder. Among the 10 participants in our phase 1 study, we had some nonresponders and moderate responders," Dr. Bydon says. "One objective in our future studies is to delineate the optimal treatment protocols and understand why patients respond differently."

In CELLTOP phase 2, 40 patients will be randomized to receive stem cell treatment or best medical management. Patients randomized to the medical management arm will eventually cross over to the stem cell arm.

Study participants must be age 18 or older and have experienced traumatic spinal cord injury within the past year. The spinal cord injuries must be American Spinal Injury Association (ASIA) grade A or B.

The initial participant in CELLTOP phase 1 sustained a C3-4 ASIA grade A spinal cord injury. As described in the February 2020 issue of Mayo Clinic Proceedings, the neurological examination at the time of the injury revealed complete loss of motor and sensory function below the level of injury.

After undergoing urgent posterior cervical decompression and fusion, as well as physical and occupational therapy, the patient demonstrated improvement in motor and sensory function. But that progress plateaued six months after the injury.

Stem cells were injected nearly a year after his injury and several months after his improvement had plateaued. Clinical signs of efficacy in both motor and sensory function were observed at three, six, 12 and 18 months following the stem cell injection.

"Our patient also reported a strong improvement with his grip and pinch strength, as well as range of motion for shoulder flexion and abduction," Dr. Bydon says.

Spinal cord injury has a complex pathophysiology. After the primary injury, microenvironmental changes inhibit axonal regeneration. Stem cells can potentially provide trophic support to the injured spinal cord microenvironment by modulating the inflammatory response, increasing vascularization and suppressing cystic change.

"In the phase 2 study, we will begin to learn the characteristics of individuals who respond to the therapy in terms of their age, severity of injury and time since injury," says Anthony J. Windebank, M.D., a neurologist at Mayo's campus in Minnesota and director of the Regenerative Neurobiology Laboratory. "We will also use biomarker studies to learn about the characteristics of responders' cells. The next phase would be studying how we can modify everyone's cells to make them more like the cells of responders."

CELLTOP illustrates Mayo Clinic's commitment to regenerative medicine therapies for neurological care. "Our findings to date will be encouraging to patients with spinal cord injuries," Dr. Bydon says. "We are hopeful about the potential of stem cell therapy to become part of treatment algorithms that improve physical function for patients with these devastating injuries."

Bydon M, et al. CELLTOP clinical trial: First report from a phase I trial of autologous adipose tissue-derived mesenchymal stem cells in the treatment of paralysis due to traumatic spinal cord injury. Mayo Clinic Proceedings. 2020;95:406.

Regenerative Neurobiology Laboratory: Anthony J. Windebank. Mayo Clinic.

Read more here:
Stem cell treatment after spinal cord injury: The next steps - Mayo Clinic

Fanconi anemia is a rare genetic disease in which essential DNA repair pathway genes are mutated, disrupting the DNA damage response. Patients with Fanconi anemia experience hematological complications, including bone marrow failure, and are predisposed to cancer. The only curative therapy for the hematological symptoms of Fanconi anemia is an allogeneic hematopoietic stem cell transplant, in which a patient receives healthy stem cells from a donor. While this may cure or prevent some of the diseases complications, stem cell transplantation can cause additional difficulties, including graft-versus-host disease (GvHD) and exacerbated cancer risk.1

There is growing interest in applying genome editing technologies like CRISPR-Cas9 to correct Fanconi anemia mutations in patient-derived cells for autologous transplants, in which corrected stem cells are given back to the patient. However, this disease poses a unique challenge: How do you apply a genome editing technique in cells that are particularly sensitive to DNA damage? Fanconi anemia cells cannot resolve the double-strand breaks that conventional CRISPR-Cas9 gene editing creates in the target DNA, which prevents researchers from effectively correcting disease-causing mutations with this method.

In a study published in International Journal of Molecular Science, a research team at the University of Minnesota led by Branden Moriarity and Beau Webber used Cas9-based tools called base editors (BEs) to edit genes in Fanconi anemia patient-derived cells without inducing double-strand DNA damage.2 BEs are fusion proteins made of a Cas9 enzyme that cleaves target DNA (nCas9) and a deaminase that converts cytidine to uridine (cytosine base editor, CBE) or adenosine to inosine (adenosine base editor, ABE). During DNA replication or repair, sites targeted by a BE are rewritten as thymine in the case of CBEs, or guanine with ABEs.

Although base editors do not induce double-strand breaks, they still nick the DNA and trigger a DNA repair response. Because of this, the researchers first examined if CBEs and ABEs would work on non-Fanconi anemia genes in patient-derived cells. There was that mystery, you know, because [Fanconi anemia patient cells are] DNA repair deficient. So we weren't surewe thought maybe it would work, but not as well as a normal cell. But indeed, it works on the same level, basically. So that was pretty exciting, Moriarity explained.

The research team then demonstrated that CBEs and ABEs can correct Fanconi anemia-causing mutations in the FANCA gene in primary patient fibroblast and lymphoblastoid cell lines. Base editing restored FANCA protein expression and improved the ability of the patient-derived cells to grow in the presence of a DNA damaging chemical. Additionally, in culture, fibroblasts with corrected FANCA mutations outgrew cells in which the base editing failed. Finally, the researchers assessed if BEs could correct mutations in different Fanconi anemia genes. Using an algorithm, they predicted that most Fanconi anemia mutations were correctable either by BEs or by another nCas9-fusion technology called prime editing (PE), which is capable of large genetic insertions and deletions.

This work comes on the heels of a preprint from another research group at The Centre for Energy, Environmental and Technological Research and ETH Zurich, who investigated ABEs in patient blood cell lines. This group also effectively targeted Fanconi anemia genes with BE technology, and their investigation went one step further: they corrected mutations in patient-derived hematopoietic stem cells.3This was something that Moriarity and Webber were unable to dobecause the disease is a bone marrow failure syndrome, these cells are scarce. Basically, these patients do not have stem cells, explains Annarita Miccio, a senior researcher and lab director at Institute Imagine of Paris Cit University, who was not involved in either study. These are very challenging experiments, and more than the experiments, the challenge of [treating] Fanconi anemia is exactly thatthe number of cells.

Despite this challenge, the researchers have laid the groundwork for genome editing as a treatment approach in Fanconi anemia, without the need for double-strand DNA breaks. I think the study we did is a good, solid proof of concept, and sets the stage for the next steps, but certainly, it's not the end of the story, said Webber.

References

Read the original:
A CRISPR Alternative for Correcting Mutations That Sensitize Cells to DNA Damage - The Scientist

As the 3rd presenter during the morning session of the American Society for Dermatologic Surgery Meeting, Emerging Concepts, Saranya Wyles, MD, PhD, assistant professor of dermatology, pharmacology, and regenerative medicine in the department of dermatology at the Mayo Clinic in Rochester, Minnesota, explored the hallmarks of skin aging, the root cause of aging and why it occurs, and regenerative medicine. Wyles first began with an explanation of how health care is evolving. In 21st-century health care, there has been a shift in how medical professionals think about medicine. Traditionally,the first approach was to fight diseases, such as cancer, inflammatory conditions, or autoimmune disorders. Now, the thought process is changing to a root cause approach with a curative option and how to rebuild health. Considering how to overcome the sequence of the different medications and treatments given to patients is rooted in regenerative medicine principles.

For skin aging, there is a molecular clock that bodies follow. Within the clock are periods of genomic instability, telomere attrition, and epigenetic alterations, and Wyles lab focuses on cellular senescence.

We've heard a lot atthis conference about bio stimulators, aesthetics, and how we can stimulate our internal mechanisms of regeneration. Now, the opposite force of regeneration isthe inhibitory aging hallmarks which include cellular senescence. So, what is cell senescence? This isa state that the cell goes into, similar to apoptosis or proliferation, where the cell goesinto a cell cycle arrest so instead of dividing apoptosis, leading to cell death,the cell stays in this zombie state, said Wyles.

Senescence occurs when bodies require a mutation for cancers. When the body recognizes there is something wrong, it launches itself into the senescent state, which can be beneficial. Alternatively, chronic senescence seen with inflammageing, like different intrinsic markers, extrinsic markers, and UV damage, is a sign of late senescence. Senescence cells can be melanocytes, fibroblasts, and cells that contribute to the regeneration of the skin.

I think were in a very exciting time ofinnovation and advancements in medicine, which is the meeting of longevity science of aging and regenerative medicine, said Wyles.

Regenerative medicine is a new field of medicine that uses native and bioengineered cells, devices, and engineering platforms with the goal of healing tissues and organs byrestoring form and function through innate mechanisms of healing.Stem cell therapy and stem cell application are commonly referenced with regenerative medicine. Typically, first-in-class treatments include cells, autologous or allogeneic, different types of cells that areassociated with high-cost due to the manufacturing.

With regenerative medicine, there's a new class of manufacturing. Regenerative medicine is not like traditional drugs where every product is consistent. These are cells, so the idea of manufacturing, and minimally manipulating, all comes into play. Now, there's a new shift towards next-generation care. This is cell-free technology. So, this is the idea of exosomes, because these are now products from cells that can be directly applied, they can be shelf-stable, accessible, and more cost-effective, said Wyles.

Exosomes are the ways that the cells communicate with each other. Cells have intercellularcommunications and depending on the source of the exosomes, there can be different signals. Wyles focused specifically on a platelet product, which is a pooled platelet product that can be purified and used for different mechanisms including wound healing, fat grafting, degenerative joint disease, and more.In a cosmetic studyconducted by Mayo Clinic, a topical platelet exosome product was applied to the face in the morning and the evening. Application included a 3-step regimen, a gentle cleanser, a platelet exosomeproduct, and then a sunscreen.

After 6 weeks, there was a significant improvement in redness and a 92% improvement in the hemoglobin process. Vasculature also improved across age groups. The study enrolled 56patients, and the average age was 54. Patients in their 40s, 50s, and 60s saw consistent improvement in redness and skin aging.

Lastly, Wyles stressed that as dermatologists think through the science-driven practices of these innovative strategies for skin aging, wound healing, and other regenerative approaches, they must think about responsible conducts of research. Currently, there are no FDA indications for exosomes being injected.

Reference:

Here is the original post:
The Switch to Regenerative Medicine - Dermatology Times

Despite being one of the most common forms of cancer, awareness of blood cancer pales in comparison to other types of the disease. In fact, according to Blood Cancer UK research, more than half of UK adults cannot name a single symptom of blood cancer.

Over the past two centuries, researchers have identified more than 100 different types of blood cancer, while most patients may be familiar with the big three (leukaemia, lymphoma, and melanoma). However, myelodysplastic syndromes and myeloproliferative neoplasms are also prominent types of blood cancer.

Thanks to the dedicated efforts of doctors, patients, carers, and healthcare professionals, people diagnosed with blood cancer are now living longer, with a steady stream of more effective treatments entering the market each year. However, there is still much to be done to achieve a vision wherein all those diagnosed with blood cancer survive.

As we enter Blood Cancer Awareness month, a global event dedicated to spotlighting and supporting efforts to improve awareness, detection, and treatment of blood cancer, we take a look back in celebration of the achievements and breakthroughs that paved the way for todays innovations.

1832 Discovery of Hodgkins and non-Hodgkins lymphoma

Although early accounts of an illness akin to leukaemia can be traced back to Ancient Greece, the first official description of blood cancer didnt appear until 1832, when British pathologist and pioneer of preventative medicine Thomas Hodgkin used the controversial concept of micrology to identify the abnormalities in the lymphatic system.

During his time working in the pathology museum at Guys Hospital in London, Hodgkin studied several preserved specimens of human organs affected by disease. Noticing a pattern in the lymph nodes and spleen that indicated the appearance of disease, he published his findings in a paper entitled, On Some Morbid Appearances of the Absorbent Glands and Spleen.

At the time, his hypothesis appeared to fall on deaf ears, and it would take a further three decades before Hodgkins discovery was recognised.

1844 First reported case of multiple myeloma

The first well-documented case of multiple myeloma was reported in 1844 by renowned British surgeon Samuel Solly. In 39-year-old patient Sarah Newbury, Solly observed the appearance of fatigue and bone pain resulting from multiple fractures. Only four years after the patient first showed symptoms, she died, and an autopsy revealed abnormalities in the bone marrow that closely matched the autopsy findings of 45-year-old Thomas Alexander McBean.

McBeans case is perhaps the most well-known account of multiple myeloma. Similar to Newbury, McBean known to be a highly respected tradesman developed fatigue and severe pain from weak and easily broken bones. After attempts to treat McBeans symptoms through cupping, applying leeches for maintenance therapy, and therapeutic phlebotomy proved unsuccessful, his physician, Dr Thomas Watson, prescribed steel and quinine, while a sample of his urine was sent to chemical pathologist Henry Bence Jones.

Following his death in 1846, histologic examination of McBeans bone marrow revealed a red gelatiniform substance consisting of nucleated cells, some twice the size of an average blood cell.

1847 Virchow links tumours and white blood cells

By the 1840s, histology (the study of microscopic anatomy) was a recognised discipline in the scientific community. Building upon early descriptions of leukaemia by French anatomist and surgeon Alfred-Armand-Louis-Marie Velpeau, in 1847, the father of modern pathology Dr Rudolf Virchow and English physician John Hughes Bennett independently observed abnormal increases in white blood cells in patients.

Virchow was the first to argue that cancer derives from changes in normal cells. Crucially, he observed a connection between certain tumours and inflammation, noting that neoplastic tissues were often covered with leukocytes of the immune system.

As with Hodgkins discovery, Virchows theory went almost unnoticed until the 20th century.

1907 The magic bullet of immunotherapy

In the early 1900s, researchers uncovered the existence of several types of blood cancer. However, effective treatments were not available at the time. During this period, Nobel prize-winning German scientist Paul Ehrlich developed his lock-key hypothesis of molecules that specifically bind to cell receptors.

Further research led Ehrlich to develop his side-chain theory, that antibodies produced by white blood cells act as receptors on the cell membrane. For his contribution, in 1908, Ehrlich received the Nobel Prize for Medicine in the field of immunology, together with the father of innate immunity, Ilia Metschnikow, whose discovery of phagocytosis formed the foundation of cell-mediated immunity.

While they may not have known it at the time, through their work Ehrlich and Metschnikow formed the cornerstone of modern immunology, including chemoreceptor and chemotherapy concepts that revolutionised blood cancer treatment over the following century.

1942 Chemotherapy moves from trenches to treatment

In the aftermath of World War I, medical researchers noticed that the mustard gas used to make chemical weapons for the battlefield also destroyed lymphatic tissue. Early experiments showed that topically applying nitrogen mustard caused tumours to shrink in mice.

Research into the medical potential of mustard gas stagnated until 1942, when two assistant professors at Yale, Louis S Goodman and Alfred Gilman, began to study the effects of nitrogen mustard on lymphoma. Although clinical trials proved that chemicals could be used to treat cancer, the results of the study remained a closely guarded military secret until 1946.

1956 The rise of bone marrow transplants

In a milestone achievement for blood cancer research and treatment, Dr E Donnall Thomas performed the first successful bone marrow transplant in 1956. The procedure involved transplanting bone marrow between identical twins, with tissue taken from the healthy twin given to the other who had leukaemia.

In 1968, the first bone marrow transplant using a matched donor took place at the University of Minnesota. Using a blood test developed by Dr Fritz Bach, Dr Robert Good determined that the patient, a baby with a severe immune deficiency, was a human leukocyte antigen match with his nine-year-old sister.

The ground-breaking approach to donor selection paved the way for future bone marrow transplants, including the first successful bone marrow transplant with unrelated patients in 1973.

Before the birth of bone marrow transplants, patients were often treated using chemotherapy, which could be used to kill cancer cells. However, this also presented a problem: chemotherapy does not discriminate between healthy and cancer cells, meaning that if patients were given sufficient doses to kill the disease, normal cells would also be harmed. With the advent of bone marrow transplantation, these healthy cells could be replaced with donor cells, allowing for higher doses of chemotherapy in treatment.

1980s Emergence of cord blood transplants

Another source of haematological stem cells emerged in the late 80s cord blood stem cells. The remaining blood found within the umbilical cord and placenta after birth is rich in blood-producing stem cells. Cord blood collection has rarely changed since the first successful procedure occurred in 1988.

Stem cells extracted from a donated cord can be frozen for a number of years and quickly accessed when needed. Once the transplant is complete, the cells will travel into the patients bone marrow, where they will begin to grow into normal blood cells.

Recognising the need to identify and match potential donors with patients, in 1989 the Bone Marrow Donors Worldwide programme was established.

Today, the bone marrow donor registry comprises more than 39,527,166 donors and 804,246 cord blood units.

2001 FDA green lights revolutionary treatments

Innovation in blood cancer treatments ushered in a new generation of targeted and precision treatments. One such therapy was Imatinib (also known as Gleevec or Glivec), a first-generation tyrosine kinase inhibitor dubbed a magical bullet, designed to specifically target BCR-ABL tyrosine kinase.

Just over a decade after it was developed by biochemist Nicholas Lyndon, Imatinib received US Food and Drug Administration (FDA) approval in 2001. Since then, it has transformed the treatment of chronic myeloid leukaemia and non-Hodgkins lymphoma.

The following year, the regulator also approved Rituximab, a monoclonal antibody targeting CD-20 positive B-cells, as a companion treatment of chemotherapy in older diffuse large B-cell lymphoma patients.

2002Emergence of CAR-T therapy

Building on the success of cytokine-based immunotherapies, scientists continued to seek other areas where the immune system could be leveraged against tumours. Throughout the 90s, Dr James Allison spearheaded research into T-cell engineering, a revolutionary technique that formed the foundation of chimeric antigen receptor (CAR) T-cell therapy.

Dr Allisons research into the function and application of T-cells in cancer treatment greatly broadened scientific understanding of the immune system. However, the first generation of CAR T-cells proved to be clinically ineffective.

It wasnt until 2002, when Memorial Sloane Kettering Cancer Center scientists Michel Sadelain, Renier Brentjens, and Isabelle Rivire opted to push the boundaries of research, by genetically engineering T-cells with a CAR, that the technique achieved successful results.

This research paved the way for the first successful treatment of a patient with acute lymphoblastic leukaemia in 2011.

2012 The 100,000 Genomics Project begins

Unlocking the secrets of the human genome has intrigued investigators for centuries. However, the technology needed to analyse genomic and long-term clinical data is a relatively recent development. With the launch of the 100,000 Genomes Project in 2012, an international team of researchers studied the role that genes play in health and disease.

For the first time, researchers demonstrated that whole genome sequencing could be used to uncover new diagnoses across the broadest range of rare diseases. This was an entirely new approach to DNA research. Previously, DNA would be segmented into short sections, which would then be read and sequenced separately.

The 100,000 Genomes Project sparked a new wave of research exploring the clinical potential of sequencing long strands of individual DNA without cutting them into sections. With this technique, it is hoped that researchers will gain previously inaccessible insights into cancer, revealing more accurate diagnoses and treatment pathways for patients.

20162022 New treatments enter the market

Over the past few years, the number of treatments approved for blood cancer has skyrocketed. Johnson & Johnsons Darzalex (daratumumab) was a notable development for the sector. The monoclonal antibody first received FDA approval in November 2015 as a monotherapy for patients with multiple myeloma, marking it as the first CD38-directed antibody to receive regulatory approval to treat the disease. It has since gone on to receive numerous approvals for multiple myeloma designations.

As of 2022, more than 800 new cell therapies are being developed for five blood cancers, with the market for oncology cell therapies expected to exceed $37 billion in value globally by 2028.

If you liked this story, check out the related video below.

Continue reading here:
A history of blood cancer treatment - - pharmaphorum

Its a fact of life: If youre lucky enough, you will get older and, with that, your body will show signs of aging. Research has been ongoing to try to determine what, exactly, is behind this process and scientists have largely linked the aging process with one biological factor: Senescent cells, aka zombie cells.

A recent study published in Nature Structural & Molecular Biology specifically links zombie cells to age-related diseases like cancer, dementia, and heart disease, and breaks down how these cells develop.

The study found the oxidative damage (damage that happens as a result of an imbalance between free radicals and antioxidants in your body) to telomeres, the protective ends of chromosomes, can spark the formation of zombie cells.

This isnt the only research on zombie cells: Scientists have been analyzing these cells and their role in aging for years.

If youve never heard of zombie cells before, fair. But, of course, you probably have someor a lot ofquestions about what these are and what role they play in aging. Heres a breakdown.

Its important to quickly recap how cells in your body work. There is a process called mitosis, which is a fundamental process for life, where a cell duplicates all of its contents and splits to form two identical cells, Medline Plus explains. When mitosis isnt regulated correctly, you can develop health problems like cancer.

Zombie cells, aka senescent cells, are cells that stop dividing, according to the National Institutes of Health (NIH). When youre younger, your immune system spots these cells and eliminates them from your body, Sabrina Barata, M.D., a primary care doctor at Mercy Personal Physicians, explains. But, as you get older, your immune system doesnt have as large of a capacity to do this.

Zombie cells simply stick around in your body. They dont diethey become resistant to death, says researcher Paul Robbins, Ph.D., associate director of the Institute on the Biology of Aging and Metabolism and the Medical Discovery Team on the Biology of Aging at the University of Minnesota. They stay in your body forever.

These cells release certain molecules that can spark inflammation and even harm other cells, Dr. Robbins says. Theyve also been linked to the growth of cancerous cells, per the NIH.

However, Dr. Robbins says, senescence is seen as an anti-cancer mechanism because it stops cells that may have become abnormal from continuing to replicate.

I would hypothesize that yes, everyone has these cells, Dr. Robbins says. Your burden of cells increases with age and older people or people with chronic diseases may have more.

Cells stop dividing after theyve divided so many times or acquire so many mutations that theyre at risk of becoming abnormal or potentially making you sick, the NIH says.

Zombie cells become more common as people age. Your immune system gets rid of these cells when youre young but, when you get older, it cant clear them as effectively, Dr. Robbins says. Research has found that tinkering with these cells can help extend lifein mice, at least.

Landmark research from Jan van Deursen, Ph.D., of the Mayo Clinic actually removed zombie cells from living mice. Van Deursen and his team discovered that injecting a certain drug triggered the death of these zombie cells.

In follow-up research, the team found that treating mice to remove zombie cells extended their median lifespans by 17% to 42%, depending on the mices sex, diet, and genetic background. The mice that were treated also usually looked healthier than those that werent treated and were more likely to have spontaneous activity and explore thingssigns of youth.

Thats what doctors think right now. If we understand why senescent cells happen and how to reverse them, we have the ability to have healthier aging with less debility, says Santosh Kesari, M.D., Ph.D., a neurologist at Providence Saint Johns Health Center in Santa Monica, Calif., and regional medical director for the Research Clinical Institute of Providence Southern Calif.

Dr. Robbins points out that zombie cells are interconnected with other things that go wrong as we age. Those include things like dysfunction in your stem cells, changes in metabolism, and dysfunction of your mitochondria, which generate energy to power your cells, he says.

If one of these things are affected, the others are, too, Dr. Robbins says. Theyre all linked. Meaning, if you can target and wipe out zombie cells, your metabolism and energy may improve, he says.

Dr. Barata says that studying these cells can absolutely help lead to advances in healthy aging. If we can find a way to kill off these cells, they wont accumulate in the body, she says. That will protect us from diseases like dementia, certain cancers, and cardiovascular disease.

Currently, research is ongoing to study the impact of targeting zombie cells and certain diseases like Alzheimers disease, osteoarthritis, and diabetes. We will know their impact quicklywithin in a few years, Dr. Robbins says

Korin Miller is a freelance writer specializing in general wellness, sexual health and relationships, and lifestyle trends, with work appearing in Mens Health, Womens Health, Self, Glamour, and more. She has a masters degree from American University, lives by the beach, and hopes to own a teacup pig and taco truck one day.

See the rest here:
What Are Zombie Cells? Here's How They Impact Aging - Prevention Magazine

Imagine a loved one on their deathbed, in need of blood stem cell therapy. If you are white you have a 79% chance of finding a match to your cell type; if you are Black you have a 29% chance. And thats not the only disparity.

This is where Erica Jensen, the senior vice president of member engagement, enrollment and experience at Be The Match, comes in.

For young white 18- to 24-year-old donors, they will be available when we call them like 67% of the time, she said. For the same age demographic, Black donors, they will be available about 29% of the time. So we have a second barrier or hurdle that we have to overcome.

Jensen described the case of 14-year-old Mikayla, a young African American teen in Minnesota who has been living with sickle cell disease (SCD). She was born with SCD, which is inherited, and has been living with the pain of it her entire life.

The only cure for SCD is a blood stem cell transplant; the donor likely needs to be someone who shares her ethnic background.

A match from the same family only happens 30% of the time.

We are trying to do everything we can to support patients like Mikayla, Jensen said.

Be The Match is a Minneapolis-based organization focused on helping people, especially the BIPOC community, find a match for blood stem cell transplants.

Be The Match realizes cancer doesnt discriminate and everyone should have access to the transplants that are necessary to live. This is what the company is striving to change by including more BIPOC employees on their staff and working with community partners, such as local churches and young adult organizations.

They also work with Future Health Professionals, or HOSA, an organization for young adults of color interested in health care, and advocate for Be the Match on TikTok and Instagram by targeting young adults.

Adding more BIPOC volunteers to the registry is one challenge but there are others.

When we find a match for you, can we get that person to commit to come in and go through the confirmatory typing that we do through a blood draw, to go through the physical exam, and then to commit to doing the actual donation process? Jensen said.

Jensen said donor safety is just as important as patient safety.

Were in the business of saving lives, she said. And were not going to risk one for the other.

Before scheduling a donation, Be The Match makes sure the donor is super healthy, able to regenerate cells with no problem and can go through the complete process.

A third challenge, Jensen said, relates to patient education. The third one, attainability, is really about the patients as to how we are making sure theres equal access to information to grants and funding, to an understanding about the cures that this can have, so that people know that they can ask, so patients can self-advocate for them to be able to get a transplant.

These reports were written by ThreeSixty Journalisms summer 2022 News Reporter Academy high school students. The academy and its theme of holistic health equity were supported by Center for Prevention at Blue Cross Blue Shield of Minnesota, which connected students with story topics and sources.

ThreeSixty Journalism is leading the way in developing multicultural storytellers in the media arts industry. The program is a loudspeaker for underheard voices, where highly motivated high school students discover the power of voice and develop their own within ThreeSixtys immersive college success programming. Launched in 1971 as an Urban Journalism Workshop chapter, since 2001 the program has been part of the College of Arts and Sciences at the University of St. Thomas. To learn more about ThreeSixty Journalism, visit threesixty.stthomas.edu.

View original post here:
ThreeSixty Journalism: Be The Match works to build equity in access to bone marrow and cord blood transplants - St. Paul Pioneer Press

Zhang wins $11.2 million NIH PPG grant to improve heart attack recovery through growth of new heart muscle cells.

Jianyi Jay Zhang, M.D., Ph.D.The National Institutes of Health has awarded a five-year, $11.2 million program project grant, or PPG, to Jianyi Jay Zhang, M.D., Ph.D., and colleagues to study how to restore the dead tissue from a heart attack, through the growth of new heart muscle cells.

That is a challenge because mammalian hearts show almost no ability to grow new heart muscle cells, called cardiomyocytes, after birth. After a heart attack from a blocked artery, the dead tissue is not repaired with new cardiomyocytes. Instead, it is replaced with scar tissue that weakens the pumping power of the heart and often leads to heart failure.

A surprising discovery by Zhang and colleagues an experimental procedure that allowed heart muscle cell growth to be extended past birth opened the door to the new research.

Recent preliminary studies from our laboratories using neonatal pigs have shown that, when a myocardial infarction is induced on postnatal day 1, or P1, cardiomyocytes reenter the cell cycle, proliferate and completely restore cardiac function with little scarring, said Zhang, chair of University of Alabama at Birmingham Department of Biomedical Engineering. Furthermore, we have found that these neonatal hearts with the P1 injury have a very active and prolonged cardiomyocyte proliferative machinery, and consequently a second left anterior descending artery ligation injury at P28 produced no visible infarct, four weeks following injury.

This was a remarkable result, as it demonstrated, for the first time, that a heart of a large mammal could remuscularize infarcted heart tissue by cardiomyocyte proliferation.

The researchers at UAB and two other universities now plan to build on this discovery through three projects. Together, the projects aim to find key pathways that allow reprogramming of adult heart muscle cells and endothelial cells, so they reenter the cell cycle and proliferate in response to a heart attack.

The first project will be led by Zhang. Its goals are first to identify the cardiomyocyte cell-cycle regulators; and second, by using the novel biotechnologies developed in Zhangs lab, to target these regulators for the purpose of making the cardiomyocytes reenter the cell cycle and proliferate, thereby remuscularizing the tissue injured during a heart attack. The findings from the large-mammal cardiac muscle regeneration will have unprecedented clinically relevant dimensions. In addition, the first project will also generate novel muscle patches made from layers of proliferating human induced pluripotent stem cells, which have activated cell-cycle regulators, and layers of other cardiac cells. Later experiments will test whether the identified factors and the patches can remuscularize the hearts of adult pigs after a heart attack.

The second project, led by Daniel J. Garry, M.D., Ph.D., University of Minnesota Medical School, will investigate whether certain effectors of the Sonic Hedgehog developmental pathway which have already been shown to induce proliferation in cultured cardiomyocytes will also be able to promote cardiomyocyte proliferation in the injured hearts of adult mice and pigs.

The third project, led by Hesham Sadek, M.D., Ph.D., University of Texas Southwestern Medical Center, Dallas, looks at the intriguing hypothesis that selective utilization of proline metabolism promotes the survival of heart ventricular myocytes and proliferation under conditions of low oxygen. That hypothesis stems from the observations that that the mammalian cell-cycle arrest in heart muscle cells is partially induced by the increase in oxygen metabolism that occurs after birth, and that severe systemic hypoxia upregulates proline metabolism and induces cardiomyocyte proliferation in adult mice.

In addition to the three projects, the grant will also fund an administrative core and a large animal core at UAB, and a bioinformatics core at the University of Minnesota Medical School.

The multi-institution National Heart, Lung, and Blood Institute grant is titled, Mechanisms that govern cardiomyocyte proliferation and remuscularization following ventricular injury.

At UAB, Biomedical Engineering is a joint department of the Marnix E. Heersink School of Medicine and the UAB School of Engineering, and Zhang holds the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership. Since Zhang came to UAB in 2015, the Department of Biomedical Engineering has grown to rank fourth nationally in NIH research funding.

Read the original post:
Zhang and colleagues win an $11.2 million NIH program project grant (PPG) - News - University of Alabama at Birmingham

Kyle Vining: Appointment to Faculty of Penn Dental Medicine and Penn School of Engineering and Applied Science

Penn Dental Medicine and the School of Engineering and Applied Science welcome recent recruit Kyle Vining, who joined the two schools and the Center for Innovation & Precision Dentistry (CiPD) on July 1, 2022. Dr. Vining is appointedan assistant professor of preventive and restorative sciences in the School of Dental Medicine and in the department of materials science and engineering in the School of Engineering and Applied Sciences, pending approval by Penn Dental Medicines personnel committees and the Provosts office.

We are thrilled that Dr. Vining has joined us, said Penn Dental Medicines Morton Amsterdam Dean Mark S. Wolff. With his combination of dental and engineering training and depth of research experience, he will play a vital role in the work and advancement of the CiPD and our goal of accelerating the development of new solutions and devices to address oral health needs.

Dr. Vining, who holds a PhD in bioengineering from Harvard University (2020) and a DDS from the University of Minnesota School of Dentistry (2014), comes to Penn Dental Medicine from the Dana-Farber Cancer Institute, where he has been a postdoctoral researcher for the past two years. A primary focus of Dr. Vinings research has been targeting mechanical regulation of tissue inflammation in bone marrow disease and head and neck cancer. He is also developing strategies to target inflammation and promote tissue repair and regeneration in oral and craniofacial diseases. Among his projects in the area of biomaterials development, he engineered a novel antimicrobial coating for titanium dental implants and developed a new polymeric dental material that supports differentiation and proliferation of dental pulp stem cells for regenerative dentistry applications. His most recent work was published in Nature Materials.

Dr. Vining has been an active research mentor to graduate and undergraduate students throughout his postdoctoral training. He is currently a councilor in the oral & maxillofacial research group of the International Association for Dental Research and is a scientific peer reviewer for 13 journals, including the American Chemical Society journals and the Journal of Dental Research.

Dr. Vining is an ideal fit for the vision and mission of the CiPD, said Penn Dental Medicines Hyun (Michel) Koo, co-director of the CiPD. With a secondary appointment in the School of Engineering, he will be instrumental in continuing to strengthen our engineering collaborations and teaching our students to work across disciplines to advance research, training, and entrepreneurship in this realm.

Kyleswork at the interface of immunology, oral health, and materials brings exciting new directions to both schools and to the CiPD, said Kathleen Stebe, co-director of the CiPD at Penn Engineering.

Shu Yang, chair of the department of materials science and engineering in the School of Engineering and Applied Science, said, Kyles research in developing novel biomaterials that interface with dental tissues and biomechanics will strengthen our leadership in biomaterials for precision health engineering.

Continued here:
Kyle Vining: Appointment to Faculty of Penn Dental Medicine and Penn School of Engineering and Applied Science - University of Pennsylvania

BOSTON--(BUSINESS WIRE)--Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapy candidates for patients with hematologic and solid cancers and other serious diseases, announces dosing of the first patient in a company-sponsored Phase 1/2 study evaluating a cryopreserved, readily available formulation of GDA-201 for the treatment of follicular and diffuse large B cell lymphomas (NCT05296525).

We are excited to further advance the development of GDA-201, a NAM-enabled natural killer (NK) cell therapy candidate which we believe has the potential to be a new readily available, cryopreserved treatment option for cancer patients with relapsed/refractory lymphoma, said Ronit Simantov, M.D., chief medical and scientific officer of Gamida Cell. Our NK cells elicited an adaptive immune response in patients in the previous investigator-sponsored study with the fresh formulation of GDA-201, potentially leading to durable remissions. We are truly grateful for the contribution of all the participants and clinical collaborators who will allow us to continue studying GDA-201 in this multi-center open label trial.

The Phase 1 portion of the study is a dose escalation phase, designed to evaluate the safety of GDA-201, and will include patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma, marginal zone lymphoma or mantle cell lymphoma. The Phase 2 expansion phase is designed to evaluate the safety and efficacy of GDA-201 in 63 patients comprised of two cohorts of patients with either FL or DLBCL. The study will include patients who have relapsed or refractory lymphoma after at least two prior treatments, which may include CAR-T or stem cell transplant.

Interest in NK cell therapies has increased in recent years as a potential alternative to current cell therapies, as NK cells have the potential to be effective in hematological and solid tumors while avoiding common safety issues, said Veronika Bachanova, M.D., Ph.D., University of Minnesota. We are particularly excited about Gamidas cryopreserved formulation of GDA-201, which has potential as a new treatment option for patients.

GDA-201 leverages Gamida Cells proprietary NAM (nicotinamide) technology platform to expand the number and functionality of NK cells to direct tumor cell killing properties and antibody-dependent cellular cytotoxicity (ADCC). In an investigator-sponsored Phase 1/2 study in patients with relapsed or refractory lymphoma, treatment with the fresh formulation of GDA-201 with rituximab demonstrated significant clinical activity. Of the 19 patients with non-Hodgkin lymphoma (NHL), 13 complete responses and one partial response were observed, with an overall response rate of 74% and a complete response rate of 68%. Two-year data on outcomes and cytokine biomarkers associated with survival data demonstrated a median duration of response of 16 months (range 5-36 months) and an overall survival at two years of 78% (95% CI, 51%91%). In this study, GDA-201 was well-tolerated and no dose-limiting toxicities were observed in 19 patients with NHL and 16 patients with multiple myeloma. The most common Grade 3/4 adverse events were thrombocytopenia, hypertension, neutropenia, febrile neutropenia, and anemia. There were no incidents of cytokine release syndrome, neurotoxic events, graft versus host disease or marrow aplasia.

About NAM Technology

Our NAM-enabled technology, supported by positive Phase 3 data for omidubicel, is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM, we can expand and metabolically modulate multiple cell types including stem cells and NK cells with appropriate growth factors to maintain the cells active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process.

About GDA-201

Gamida Cell applied the capabilities of its NAM-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy candidate for the treatment of hematologic and solid tumors in combination with standard-of-care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical trial results. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, GDA-201 improves ADCC and tumor targeting of NK cells. There are approximately 40,000 patients with relapsed/refractory lymphoma in the US and EU, which is the patient population that will be studied in the currently ongoing GDA-201 Phase 1/2 clinical trial.

For more information about GDA-201, please visit https://www.gamida-cell.com. For more information on the Phase 1/2 clinical trial of GDA-201, please visit http://www.clinicaltrials.gov.

GDA-201 is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

About Gamida Cell

Gamida Cell is pioneering a diverse immunotherapy pipeline of potentially curative cell therapy candidates for patients with solid tumor and blood cancers and other serious blood diseases. We apply a proprietary expansion platform leveraging the properties of NAM to allogeneic cell sources including umbilical cord blood-derived cells and NK cells to create therapy candidates with potential to redefine standards of care. These include omidubicel, an investigational product with potential as a life-saving alternative for patients in need of bone marrow transplant, and a line of modified and unmodified NAM-enabled NK cells targeted at solid tumor and hematological malignancies. For additional information, please visit http://www.gamida-cell.com or follow Gamida Cell on LinkedIn, Twitter, Facebook or Instagram at @GamidaCellTx.

Cautionary Note Regarding Forward Looking Statements

This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including with respect to: the timing of initiation of the expansion portion of the currently ongoing Phase 1/2 clinical trial of GDA-201, as well as the progress of, and data reported from, this clinical trial; the potentially life-saving or curative therapeutic and commercial potential of Gamida Cells product candidates (including omidubicel and GDA-201); and Gamida Cells expectations for the expected clinical development milestones set forth herein. Any statement describing Gamida Cells goals, expectations, or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to a number of risks, uncertainties and assumptions, including statements related to: the impact that the COVID-19 pandemic could have on our business; the scope, progress and expansion of Gamida Cells clinical trials and ramifications for the cost thereof; clinical, scientific, regulatory and technical developments; the process of developing and commercializing product candidates that are safe and effective for use as human therapeutics; and the endeavor of building a business around such product candidates. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section and other sections of Gamida Cells Quarterly Report on Form 10-Q, filed with the Securities and Exchange Commission (SEC) on May 12, 2022, and other filings that Gamida Cell makes with the SEC from time to time (which are available at http://www.sec.gov), the events and circumstances discussed in such forward-looking statements may not occur, and Gamida Cells actual results could differ materially and adversely from those anticipated or implied thereby. Although Gamida Cells forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Gamida Cell. As a result, you are cautioned not to rely on these forward-looking statements.

Follow this link:
Gamida Cell Announces Dosing of First Patient in Company-Sponsored Phase 1/2 Study of NK Cell Therapy Candidate GDA-201 - Business Wire

A University of Minnesota Twin Cities team has developed a new tool to predict and customize the rate of a specific kind of DNA editing called site-specific recombination. The research, recently published in Nature Communications,paves the way for more personalized, efficient genetic and cell therapies for diseases such as diabetes and cancer.

The process of site-specific recombination involves using enzymes that recognize and modify specific sequences of DNA in living cells. It has important applications in cellular therapies used to treat myriad diseases.

U of M engineers developed a method that makes the site-specific recombination process more efficient and predictable. The model allows researchers to program the rate at which the DNA is edited, which means they can control the speed at which a therapeutic cell responds to its environment, thereby controlling how quickly or slowly it produces a drug or therapeutic protein.

To our knowledge, this is the first example of using a model to predict how modifying a DNA sequence can control the rate of site-specific recombination, said Casim Sarkar, senior author on the paper and an associate professor in the U of M Department of Biomedical Engineering. By applying engineering principles to this problem, we can dial in the rate at which DNA editing happens and use this form of control to tailor therapeutic cellular responses. Our study also identified novel DNA sequences that are much more efficiently recombined than those found in nature, which can accelerate cellular response times.

Sarkar and his team first developed an experimental method to calculate the rate of site-specific recombination, then used that information to train a machine learning algorithm. Ultimately, this allows the researchers to simply type in a DNA sequence and have the model predict the rate at which that DNA sequence will be recombined.

They also found that they could use modeling to predict and control the simultaneous production of multiple proteins within a cell. This could be used to program stem cells to produce new tissues or organs for regenerative medicine applications or to endow therapeutic cells with the ability to produce multiple drugs in pre-defined proportions.

This research was funded by the National Institutes of Health.

-30-

About the College of Science and EngineeringThe University of Minnesota College of Science and Engineering brings together the Universitys programs in engineering, physical sciences, mathematics and computer science into one college. The college is ranked among the top academic programs in the country and includes 12 academic departments offering a wide range of degree programs at the baccalaureate, master's, and doctoral levels. Learn more at cse.umn.edu.

Read the original here:
Engineers develop new tool that will allow for more personalized cell therapies - UMN News