diabetes

Two Early-Stage Research Programs Targeting Cartilage Damage Get Funding from Stem Cell Agency

/ Kevin McCormack / 1 Comment

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Darryl D’Lima: Scripps Health

Every year millions of Americans suffer damage to their cartilage, either in their knee or other joints, that can eventually lead to osteoarthritis, pain and immobility. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two projects targeting repair of damaged cartilage.

The projects were among 17 approved by CIRM as part of the DISC2 Quest Discovery Program. The program promotes the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.

Dr. Darryl D’Lima and his team at Scripps Health were awarded $1,620,645 to find a way to repair a torn meniscus. Every year around 750,000 Americans experience a tear in their meniscus, the cartilage cushion that prevents the bones in the knee grinding against each other. These injuries accelerate the early development of osteoarthritis, for which there is no effective treatment other than total joint replacement, which is a major operation. There are significant socioeconomic benefits to preventing disabling osteoarthritis. The reductions in healthcare costs are also likely to be significant.

The team will use stem cells to produce meniscal cells in the lab. Those are then seeded onto a scaffold made from collagen fibers to create tissue that resembles the knee meniscus. The goal is to show that, when placed in the knee joint, this can help regenerate and repair the damaged tissue.

This research is based on an earlier project that CIRM funded. It highlights our commitment to helping good science progress, hopefully from the bench to the bedside where it can help patients.

Dr. Kevin Stone: Photo courtesy Stone Research Foundation

Dr. Kevin Stone and his team at The Stone Research Foundation for Sports Medicine and Arthritis were awarded $1,316,215 to develop an approach to treat and repair damaged cartilage using a patient’s own stem cells.

They are using a paste combining the patient’s own articular tissue as well as Mesenchymal Stem Cells (MSC) from their bone marrow. This mixture is combined with an adhesive hydrogel to form a graft that is designed to support cartilage growth and can also stick to surfaces without the need for glue. This paste will be used to augment the use of a microfracture technique, where micro-drilling of the bone underneath the cartilage tear brings MSCs and other cells to the fracture site. The hope is this two-pronged approach will produce an effective and functional stem cell-based cartilage repair procedure.

If effective this could produce a minimally invasive, low cost, one-step solution to help people with cartilage injuries and arthritis.

The full list of DISC2 grantees is:

ApplicationTitlePrincipal Investigator and InstitutionAmount
DISC2-13212Preclinical development of an exhaustion-resistant CAR-T stem cell for cancer immunotherapy  Ansuman Satpathy – Stanford University    $ 1,420,200  
DISC2-13051Generating deeper and more durable BCMA CAR T cell responses in Multiple Myeloma through non-viral knockin/knockout multiplexed genome engineering  Julia Carnevale – UC San Francisco  $ 1,463,368  
DISC2-13020Injectable, autologous iPSC-based therapy for spinal cord injury  Sarah Heilshorn – Stanford University    $789,000
DISC2-13009New noncoding RNA chemical entity for heart failure with preserved ejection fraction.  Eduardo Marban – Cedars-Sinai Medical Center  $1,397,412  
DISC2-13232Modulation of oral epithelium stem cells by RSpo1 for the prevention and treatment of oral mucositis  Jeffrey Linhardt – Intact Therapeutics Inc.  $942,050  
DISC2-13077Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)  Mathew Blurton-Jones – UC Irvine    $1,199,922  
DISC2-13201Matrix Assisted Cell Transplantation of Promyogenic Fibroadipogenic Progenitor (FAP) Stem Cells  Brian Feeley – UC San Francisco  $1,179,478  
DISC2-13063Improving the efficacy and tolerability of clinically validated remyelination-inducing molecules using developable combinations of approved drugs  Luke Lairson – Scripps Research Inst.  $1,554,126  
DISC2-13213Extending Immune-Evasive Human Islet-Like Organoids (HILOs) Survival and Function as a Cure for T1D  Ronald Evans – The Salk Institute for Biological Studies    $1,523,285  
DISC2-13136Meniscal Repair and Regeneration  Darryl D’Lima – Scripps Health      $1,620,645  
DISC2-13072Providing a cure for sphingosine phosphate lyase insufficiency syndrome (SPLIS) through adeno-associated viral mediated SGPL1 gene therapy  Julie Saba – UC San Francisco  $1,463,400  
DISC2-13205iPSC-derived smooth muscle cell progenitor conditioned medium for treatment of pelvic organ prolapse  Bertha Chen – Stanford University  $1,420,200  
DISC2-13102RNA-directed therapy for Huntington’s disease  Gene Wei-Ming Yeo  – UC San Diego  $1,408,923  
DISC2-13131A Novel Therapy for Articular Cartilage Autologous Cellular Repair by Paste Grafting  Kevin Stone – The Stone Research Foundation for Sports Medicine and Arthritis    $1,316,215  
DISC2-13013Optimization of a gene therapy for inherited erythromelalgia in iPSC-derived neurons  Ana Moreno – Navega Therapeutics    $1,157,313  
DISC2-13221Development of a novel stem-cell based carrier for intravenous delivery of oncolytic viruses  Edward Filardo – Cytonus Therapeutics, Inc.    $899,342  
DISC2-13163iPSC Extracellular Vesicles for Diabetes Therapy  Song Li – UC Los Angeles  $1,354,928  

UCSF Nursing Professor Joins CIRM Board

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Elena Flowers, PhD, RN, newest member of the CIRM Board: Photo courtesy UCSF

Elena Flowers, PhD, RN, an associate professor of physiological nursing at the University of California, San Francisco (UCSF) is joining the Board of the California Institute for Regenerative Medicine (CIRM), the state’s Stem Cell Agency.

Dr. Flowers was appointed to the Board by State Controller Betty T. Yee who said: “Ms. Flowers’ experience and express commitment to equitable health outcomes for California’s diverse communities will bring a valued perspective to the work ahead.”

Dr. Flowers is a member of the UCSF Institute for Human Genetics and the International Society of Nurses in Genetics. As a researcher her work focuses on genomics involving precision medicine and risk factors for cardiovascular health and type 2 diabetes. She is also a teacher and has lectured internationally on issues such as topics from racial disparities in Type 2 Diabetes to the implications of genomic technologies for the nursing workforce.

CIRM Board Chair, Jonathan Thomas, PhD, JD, welcomed the appointment: “Dr. Flowers brings a wealth of experience and expertise to our Board and, as a nurse, she will bring a different perspective to the work we do and help us in trying to better address the needs of underserved communities.” 

“I am honored to have the opportunity to serve the citizens of California in this capacity,” says Dr. Flowers. “CIRM has ambitious goals, seeking to improve upon common limitations of public research agencies by its commitment to delivering meaningful findings and ultimately treatments for patients as rapidly as possible. I’m particularly committed to improving inclusion and access to these treatments across the entire diverse California population.”

Dr. Flowers got her undergraduate degree at UC Davis and then served as a research assistant at Zuckerberg San Francisco General Hospital. She then went on to get her MS and Doctor of Philosophy degrees at the UCSF School of Nursing.

In her spare time she has no spare time because she is the mother of two young daughters.

The Most Important Gift of All

/ Kevin McCormack / Leave a comment
Photo courtesy American Hospital Association

There are many players who have a key role in helping make a stem cell therapy work. The scientists who develop the therapy, the medical team who deliver it and funders like CIRM who provide the money to make this all happen. But vital as they are, in some therapies there is another, even more important group; the people who donate life-saving organs and tissues for transplant and research.

Organ and tissue donation saves lives, increases knowledge of diseases, and allow for the development of novel medications to treat them. When individuals or their families authorize donation for transplant or medical research, they allow their loved ones to build a long-lasting legacy of hope that could not be accomplished in any other way.

Four of CIRM’s clinical trials involve organ donations – three kidney transplant programs (you can read about those here, here and here) and one targeting type 1 diabetes.

Dr. Nikole Neidlinger, the Chief Medical Officer with Donor Network West – the federally designated organ and tissue recovery organization for Northern California and Nevada – says it is important to recognize the critical contribution made in a time of grief and crisis by the families of deceased donors. 

“For many families who donate, a loved one has died, and they are in shock. Even so, they are willing to say yes to giving others a second chance at life and to help others to advance science. Without them, none of this would be possible. It’s the ultimate act of generosity and compassion.”

The latest CIRM-funded clinical trial involving donated tissue is with Dr. Peter Stock and his team at UCSF. They are working on a treatment for type 1 diabetes (T1D), where the body’s immune system destroys its own pancreatic beta cells. These cells are necessary to produce insulin, which regulates blood sugar levels in the body.

In the past people have tried transplanting beta cells, from donated pancreatic islets, into patients with type 1 diabetes to try and reverse the course of the disease. However, this requires islets from multiple donors and the shortage of organ and tissue donors makes this difficult to do.

Dr. Stock’s clinical trial at UCSF aims to address these limitations.  He is going to transplant both pancreatic islets and parathyroid glands, from the same donor, into T1 patients. It’s hoped this combination approach will increase beta cell survival, potentially boosting long-term insulin production and removing the need for multiple donors.  And because the transplant is placed in the patient’s forearm, it makes it easier to monitor the effectiveness and accessibility of the islet transplants. Of equal importance, the development of this site will facilitate the transplantation of stem cell derived beta cells, which are very close to clinical application.

“As a transplant surgeon, it is an absolute privilege to be able to witness the life-saving organ transplants made possible by the selfless generosity of the donor families. It is hard to imagine how families have the will to think about helping others at a time of their greatest grief. It is this willingness to help others that restores my faith in humanity”

Donor Network West plays a vital role in this process. In 2018 alone, the organization recovered 702 donor samples for research. Thanks to the generosity of the donors/donor families, the donor network has been able to provide parathyroid and pancreas tissue essential to make this clinical trial a success”

“One organ donor can save the lives of up to eight people and a tissue donor can heal more than 75 others,” says Dr. Neidlinger. “For families, the knowledge that they are transforming someone’s life, and possibly preventing another family from experiencing this same loss, can serve as a silver lining during their time of sorrow. .”

Organs that can be donated

Kidney (x2), Heart, Lungs (x2), Liver, Pancreas, Intestine

Tissue that can be donated

Corneas, Heart valves, Skin, Bone, Tendons, Cartilage, Veins

Currently, there are over 113,000 people in the U.S. waiting for an organ transplant, of which 84 % are in need of kidneys.  Sadly, 22 people die every day waiting for an organ transplant that does not come in time. The prospect of an effective treatment for type 1 diabetes means hope for thousands of people living with the chronic condition.

Predicting the Impact of Stem Cell Cures on Healthcare Burden in California

/ Kevin McCormack / Leave a comment

A new independent report says developing stem cell treatments and cures for some of the most common and deadly diseases could produce multi-billion dollar benefits for California in reduced healthcare costs and improved quality and quantity of life.

The report, by researchers at the University of Southern California’s Leonard D. Schaeffer Center for Health Policy & Economics, looked at the value of hypothetical future interventions to reduce or cure cancer, diabetes, stroke and blindness.

Predicting the future is always complicated and uncertain and many groups are looking at the best models to determine the value and economic impact of cell and gene therapy as the first products are just entering the market. This study provides some insights into the potential financial benefits of developing effective stem cell treatments for some of the most intractable diseases affecting California today.

The impact could affect millions of people. In 2018 for Californians over the age of 50:

  • Nearly half were predicted to develop diabetes in their lifetime
  • More than one third will experience a stroke
  • Between 5 and 8 percent will develop either breast, colorectal, lung, or prostate cancer

The report says that a therapy that decreased the incidence of diabetes by 50 percent in Californians over the age of 51 would translate into a gain for the state of $322 billion in social value between now and 2050. Even just reducing diabetes 10% would lead to a gain of $60 billion in social value over the same period.

  • For stroke a 50 percent reduction would generate an estimated $229 billion in social value. A 10 percent reduction would generate $47 billion
  • For breast cancer a 50 percent reduction would generate $56 billion in social value; for colorectal cancer it would be $72 billion; for lung cancer $151 billion; and prostate cancer $53 billion. 

The impact of a cure for any one of those diseases would be enormous. For example, a 51-year-old woman cured of lung cancer could expect to gain a lifetime social value of almost half a million dollars ($467,275). That’s a measure of years of healthy life gained, of years spent enjoying time with family and friends and not wasting away or lying in a hospital bed.

The researchers say: “Though advances in scientific research defy easy predictions, investing in biomedical research is important if we want to reduce the burden of common and costly diseases for individuals, their families, and society. These findings show the value and impact breakthrough treatments could have for California.”

“Put in this context, the CIRM investment would be worthwhile if it increased our chances of success even modestly. Against the billions of dollars in disease burden facing California, the relatively small initial investment is already paying dividends as researchers work to bring new therapies to patients.”

The researchers determined the “social value” using a measure called a quality adjusted life-year (QALY). This is a way of estimating the cost effectiveness and consequences of treating or not treating a disease. For example, one QALY is equivalent to one year of perfect health for an individual. In this study the value of that year was estimated at $150,000. If someone is sick with, say, diabetes, their health would be estimated to be 0.5 QALY or $75,000. So, the better health a person enjoys and the longer they enjoy it the higher QALY score they accumulate. In the case of a disease affecting millions of people in that state or country that can obviously lead to very large QALY scores representing potentially billions of dollars.

Moving a great idea targeting diabetes out of the lab and into a company

/ Kevin McCormack / 3 Comments
Tejal Desai in her lab at UCSF: Photo courtesy Todd Dubnicoff

It’s always gratifying to see research you have helped support go from being an intriguing idea to something with promise to a product that is now the focus of a company. It’s all the more gratifying if the product in question might one day help millions of people battling diabetes.

That’s the case with a small pouch being developed by a company called Encellin. The pouch is the brainchild of Tejal Desai, Ph.D., a professor of bioengineering at UCSF and a CIRM grantee.

Encellin’s encapsulation device

“It’s a cell encapsulation device, so this material can essentially protect beta cells from the immune system while allowing them to function by secreting insulin. We are placing stem cell-derived beta cells into the pouch which is then implanted under the skin. The cells are then able to respond to changes in sugar or glucose levels in the blood by pumping out insulin.  By placing the device in a place that is accessible we can easily remove it if we have to, but also we can recharge it and put in new cells as well.”

While the pouch was developed in Dr. Desai’s lab, the idea to take it from a promising item and try to turn it into a real-world therapy came from one of Dr. Desai’s former students, Crystal Nyitray, Ph.D.

Crystal Nyitray: Photo courtesy FierceBiotech

After getting her PhD, Nyitray went to work for the pharmaceutical giant Sanofi. In an article in FierceBiotech she says that’s where she realized that the pouch she had been working on at UCSF had real potential.

“During that time, I started to realize we really had something, that everything that pharma or biotech was looking at was something we had been developing from the ground up with those specific questions in mind,”

So Dr. Nyitray went to work for QB3, the institute created by UC San Francisco to help startups develop their ideas and get funding. The experience she gained there gave her the confidence to be the co-founder and CEO of Encellin.

Dr. Desai is a scientific advisor to Encellin. She says trying to create a device that contains insulin-secreting cells is not new. Many previous attempts failed because once the device was placed in the body, the immune system responded by creating fibrosis or scarring around it which blocked the ability of the cells to get out.

But she thinks their approach has an advantage over previous attempts.

“This is not a new idea, the idea has been around for 40 or more years but getting it to work is hard. We have a convergence of getting the right cell types and combining that with our knowledge of immunology and then the material science where we can design materials at this scale to get the kind of function that we need.

Dr. Nyitray ““If we can reduce fibrosis, it really helps the cells get nutrients better, survive better and signal more effectively. It’s really critical to their success.”

Dr. Desai says the device is still in the early stages of being tested, but already it’s showing promise.

“We have done testing in animals. Where the company is taking this is now to see if we can take this to larger animals and then ultimately people.”

She says without CIRM’s support none of this would have happened.

“CIRM has been really instrumental in helping us refine the cell technology piece of it, to get really robust cells and also to support the development to push the materials, to understand the biology, to really understand what was happening with the cell material interface. We know we have a lot of challenges ahead, but we are really excited to see if this could work.”

We are excited too. We are looking forward to seeing what Encellin does in the coming years. It could change the lives of millions of people around the world.

No pressure. 

Rare Disease Gets Big Boost from California’s Stem Cell Agency

/ Kevin McCormack / 4 Comments
UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

Stem Cell Agency Heads to Inland Empire for Free Patient Advocate Event

/ Kevin McCormack / 2 Comments

UCRiversidePatientAdvocateMtg_EventBrite copy

I am embarrassed to admit that I have never been to the Inland Empire in California, the area that extends from San Bernardino to Riverside counties.  That’s about to change. On Monday, April 16th CIRM is taking a road trip to UC Riverside, and we’re inviting you to join us.

We are holding a special, free, public event at UC Riverside to talk about the work that CIRM does and to highlight the progress being made in stem cell research. We have funded 45 clinical trials in a wide range of conditions from stroke and cancer, leukemia, lymphoma, vision loss, diabetes and sickle cell disease to name just a few. And will talk about how we plan on funding many more clinical trials in the years to come.

We’ll be joined by colleagues from both UC Riverside, and City of Hope, talking about the research they are doing from developing new imaging techniques to see what is happening inside the brain with diseases like Alzheimer’s, to using a patient’s own cells and immune system to attack deadly brain cancers.

It promises to be a fascinating event and of course we want to hear from you, our supporters, friends and patient advocates. We are leaving plenty of time for questions, so we can hear what’s on your mind.

So, join us at UC Riverside on Monday, April 16th from 12.30pm to 2pm. The doors open at 11am so you can enjoy a poster session (highlighting some of the research at UCR) and a light lunch before the event. Parking will be available on site.

Visit the Eventbrite page we have created for all the information you’ll need about the event, including a chance to RSVP and book your place.

The event is free so feel free to share this with anyone and everyone you think might be interested in joining us.

 

 

CIRM-Funded Research Makes Multiple Headlines this Week

/ Karen Ring / Leave a comment

When it rains it pours.

This week, multiple CIRM-funded studies appeared in the news, highlighting the exciting progress our Agency is making towards funding innovative stem cell research and promoting the development of promising stem cell therapies for patients.

Below are highlights.

Fate Therapeutics Partners with UC San Diego to Develop Cancer Immunotherapy

Last week, Dr. Dan Kaufman and his team at UC San Diego, received a $5.15 million therapeutic translational research award from CIRM to advance the clinical development of a stem cell-derived immunotherapy for acute myelogenous leukemia (AML), a rare form of blood cancer.

Today, it was announced that the UCSD team is entering into a research collaboration with a San Diego biopharmaceutical company Fate Therapeutics to develop a related immunotherapy for blood cancers. The therapy consists of immune cells called chimeric antigen receptor-targeted natural killer (CAR NK) cells that can target tumor cells and stop their growth. Fate Therapeutics has developed an induced pluripotent stem cell (iPSC) platform to develop and optimize CAR NK cell therapies targeting various cancers.

According to an article by GenBio, this new partnership is already bearing fruit.

“In preclinical studies using an ovarian cancer xenograft model, Dr. Kaufman and Fate Therapeutics had shown that a single dose of CAR-targeted NK cells derived from iPSCs engineered with the CAR construct significantly inhibited tumor growth and increased survival compared to NK cells containing a CAR construct commonly used for T-cell immunotherapy.”

 

City of Hope Brain Cancer Trial Featured as a Key Trial to Watch in 2018

Xconomy posted a series this week forecasting Key Clinical Data to look out for next year. Today’s part two of the series mentioned a recent CIRM-funded trial for glioblastoma, an aggressive, deadly brain cancer.

Christine Brown and her team at the City of Hope are developing a CAR-T cell therapy that programs a patient’s own immune cells to specifically target and kill cancer cells, including cancer stem cells, in the brain. You can read more about this therapy and the Phase 1 trial on our website.

Alex Lash, Xconomy’s National Biotech Editor, argued that good results for this trial would be a “huge step forward for CAR-T”.

Alex Lash

“While CAR-T has proven its mettle in certain blood cancers, one of the biggest medical questions in biotech is whether the killer cells can also eat up solid tumors, which make up the majority of cancer cases. Glioblastoma—an aggressive and usually incurable brain cancer—is a doozy of a solid tumor.”

ViaCyte Receives Innovative New Product Award for Type 1 Diabetes

Last week, San Diego-based ViaCyte was awarded the “Most Innovative New Product Award” by CONNECT, a start-up accelerator focused on innovation, for its PEC-Direct product candidate. The product is a cell-based therapy that’s currently being tested in a CIRM-funded clinical trial for patients with high-risk type 1 diabetes.

In a company news release published today, ViaCyte’s CEO Paul Laikind commented on what the award signifies,

Paul Laikind

“This award acknowledges how ViaCyte has continually broken new ground in stem cell research, medical device engineering, and cell therapy scaling and manufacturing. With breakthrough technology, clinical stage product candidates, an extensive intellectual property estate, and a strong and dedicated team, ViaCyte has all the pieces to advance a transformative new life-saving approach that could help hundreds of thousands of people with high-risk type 1 diabetes around the world.”

Stories that caught our eye: How dying cells could help save lives; could modified blood stem cells reverse diabetes?; and FDA has good news for patients, bad news for rogue clinics

/ Kevin McCormack / Leave a comment

Gunsmoke

Growing up I loved watching old cowboy movies. Invariably the hero, even though mortally wounded, would manage to save the day and rescue the heroine and/or the town.

Now it seems some stem cells perform the same function, dying in order to save the lives of others.

Researchers at Kings College in London were trying to better understand Graft vs Host Disease (GvHD), a potentially fatal complication that can occur when a patient receives a blood stem cell transplant. In cases of GvHD, the transplanted donor cells turn on the patient and attack their healthy cells and tissues.

Some previous research had found that using bone marrow cells called mesenchymal stem cells (MSCs) had some success in combating GvHD. But it was unpredictable who it helped and why.

Working with mice, the Kings College team found that the MSCs were only effective if they died after being transplanted. It appears that it is only as they are dying that the MSCs engage with the individual’s immune system, telling it to stop attacking healthy tissues. The team also found that if they kill the MSCs just before transplanting them into mice, they were just as effective.

In a news article on HealthCanal, lead researcher Professor Francesco Dazzi, said the next step is to see if this will apply to, and help, people:

“The side effects of a stem cell transplant can be fatal and this factor is a serious consideration in deciding whether some people are suitable to undergo one. If we can be more confident that we can control these lethal complications in all patients, more people will be able to receive this life saving procedure. The next step will be to introduce clinical trials for patients with GvHD, either using the procedure only in patients with immune systems capable of killing mesenchymal stem cells, or killing these cells before they are infused into the patient, to see if this does indeed improve the success of treatment.”

The study is published in Science Translational Medicine.

Genetically modified blood stem cells reverse diabetes in mice (Todd Dubnicoff)

When functioning properly, the T cells of our immune system keep us healthy by detecting and killing off infected, damaged or cancerous cells in our body. But in the case of type 1 diabetes, a person’s own T cells turn against the body by mistakenly targeting and destroying perfectly normal islet cells in the pancreas, which are responsible for producing insulin. As a result, the insulin-dependent delivery of blood sugar to the energy-hungry organs is disrupted leading to many serious complications. Blood stem cell transplants have been performed to treat the disease by attempting to restart the immune system. The results have failed to provide a cure.

Now a new study, published in Science Translational Medicine, appears to explain why those previous attempts failed and how some genetic rejiggering could lead to a successful treatment for type 1 diabetes.

An analysis of the gene activity inside the blood stem cells of diabetic mice and humans reveals that these cells lack a protein called PD-L1. This protein is known to play an important role in putting the brakes on T cell activity. Because T cells are potent cell killers, it’s important for proteins like PD-L1 to keep the activated T cells in check.

Cell based image for t 1 diabetes

Credit: Andrea Panigada/Nancy Fliesler

Researchers from Boston Children’s Hospital hypothesized that adding back PD-L1 may prevent T cells from the indiscriminate killing of the body’s own insulin-producing cells. To test this idea, the research team genetically engineered mouse blood stem cells to produce the PD-L1 protein. Experiments with the cells in a petri dish showed that the addition of PD-L1 did indeed block the attack-on-self activity. And when these blood stem cells were transplanted into a diabetic mouse strain, the disease was reversed in most of the animals over the short term while a third of the mice had long-lasting benefits.

The researchers hope this targeting of PD-L1 production – which the researchers could also stimulate with pharmacological drugs – will contribute to a cure for type 1 diabetes.

FDA’s new guidelines for stem cell treatments

Gottlieb

FDA Commissioner Scott Gottlieb

Yesterday Scott Gottlieb, the Commissioner at the US Food and Drug Administration (FDA), laid out some new guidelines for the way the agency regulates stem cells and regenerative medicine. The news was good for patients, not so good for clinics offering unproven treatments.

First the good. Gottlieb announced new guidelines encouraging innovation in the development of stem cell therapies, and faster pathways for therapies, that show they are both safe and effective, to reach the patient.

At the same time, he detailed new rules that provide greater clarity about what clinics can do with stem cells without incurring the wrath of the FDA. Those guidelines detail the limits on the kinds of procedures clinics can offer and what ways they can “manipulate” those cells. Clinics that go beyond those limits could be in trouble.

In making the announcement Gottlieb said:

“To be clear, we remain committed to ensuring that patients have access to safe and effective regenerative medicine products as efficiently as possible. We are also committed to making sure we take action against products being unlawfully marketed that pose a potential significant risk to their safety. The framework we’re announcing today gives us the solid platform we need to continue to take enforcement action against a small number of clearly unscrupulous actors.”

Many of the details in the announcement match what CIRM has been pushing for some years. Randy Mills, our previous President and CEO, called for many of these changes in an Op Ed he co-wrote with former US Senator Bill Frist.

Our hope now is that the FDA continues to follow this promising path and turns these draft proposals into hard policy.

 

Stem Cell Stories that Caught Our Eye: New law to protect consumers; using skin to monitor blood sugar; and a win for the good guys

/ Kevin McCormack / Leave a comment

Hernendez

State Senator Ed Hernandez

New law targets stem cell clinics that offer therapies not approved by the FDA

For some time now CIRM and others around California have been warning consumers about the risks involved in going to clinics that offer stem cell therapies that have not been tested in a clinical trial or approved by the U.S. Food and Drug Administration (FDA) for use in patients.

Now a new California law, authored by State Senator Ed Hernandez (D-West Covina) attempts to address that issue. It will require medical clinics whose stem cell treatments are not FDA approved, to post notices and provide handouts to patients warning them about the potential risk.

In a news release Sen. Hernandez said he hopes the new law, SB 512, will protect consumers from early-stage, unproven experimental therapies:

“There are currently over 100 medical offices in California providing non-FDA approved stem cell treatments. Patients spend thousands of dollars on these treatments, but are totally unaware of potential risks and dangerous side effects.”

Sen. Hernandez’s staffer Bao-Ngoc Nguyen crafted the bill, with help from CIRM Board Vice Chair Sen. Art Torres, Geoff Lomax and UC Davis researcher Paul Knoepfler, to ensure it targeted only clinics offering non-FDA approved therapies and not those offering FDA-sanctioned clinical trials.

For example the bill would not affect CIRM’s Alpha Stem Cell Clinic Network because all the therapies offered there have been given the green light by the FDA to work with patients.

Blood_Glucose_Testing 

Using your own skin as a blood glucose monitor

One of the many things that people with diabetes hate is the constant need to monitor their blood sugar level. Usually that involves a finger prick to get a drop of blood. It’s simple but not much fun. Attempts to develop non-invasive monitors have been tried but with limited success.

Now researchers at the University of Chicago have come up with another alternative, using the person’s own skin to measure their blood glucose level.

Xiaoyang Wu and his team accomplished this feat in mice by first creating new skin from stem cells. Then, using the gene-editing tool CRISPR, they added in a protein that sticks to sugar molecules and another protein that acts as a fluorescent marker. The hope was that the when the protein sticks to sugar in the blood it would change shape and emit fluorescence which could indicate if blood glucose levels were too high, too low, or just right.

The team then grafted the skin cells back onto the mouse. When those mice were left hungry for a while then given a big dose of sugar, the skin “sensors” reacted within 30 seconds.

The researchers say they are now exploring ways that their findings, published on the website bioRxiv, could be duplicated in people.

While they are doing that, we are supporting ViaCytes attempt to develop a device that doesn’t just monitor blood sugar levels but also delivers insulin when needed. You can read about our recent award to ViaCyte here.

Deepak

Dr. Deepak Srivastava

Stem Cell Champion, CIRM grantee, and all-round-nice guy named President of Gladstone Institutes

I don’t think it would shock anyone to know that there are a few prima donnas in the world of stem cell research. Happily, Dr. Deepak Srivastava is not one of them, which makes it such a delight to hear that he has been appointed as the next President of the Gladstone Institutes in San Francisco.

Deepak is a gifted scientist – which is why we have funded his work – a terrific communicator and a really lovely fella; straight forward and down to earth.

In a news release announcing his appointment – his term starts January 1 next year – Deepak said he is honored to succeed the current President, Sandy Williams:

“I joined Gladstone in 2005 because of its unique ability to leverage diverse basic science approaches through teams of scientists focused on achieving scientific breakthroughs for mankind’s most devastating diseases. I look forward to continue shaping this innovative approach to overcome human disease.”

We wish him great success in his new role.