Stem Cell Agency Board Invests in 19 Discovery Research Programs Targeting Cancers, Heart Disease and Other Disorders

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Dr. Judy Shizuru, Stanford University

While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.

The awards are from CIRM’s DISC2 Quest program, which supports  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.

“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”

Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.

Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics

Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.

Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.

In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.

Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.

Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.

The full list of DISC2 Quest awards is:

APPLICATION NUMBERTITLE OF PROGRAMPRINCIPAL INVESTIGATORAMOUNT
  DISC2-13400  Targeted Immunotherapy-Based Blood Stem Cell Transplantation    Judy Shizuru, Stanford Universtiy  $1,341,910    
  DISC2-13505  Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells    Lili Yang, UCLA  $1,404,000
  DISC2-13515  A treatment for Rett syndrome using glial-restricted
neural progenitor cells  
  Alysson Muotri, UC San Diego  $1,402,240    
  DISC2-13454  Targeting pancreatic cancer stem cells with DDR1 antibodies.    Michael Karin, UC San Diego  $1,425,600  
  DISC2-13483  Enabling non-genetic activity-driven maturation of iPSC-derived neurons    Alex Savtchenko, Nanotools Bioscience  $675,000
  DISC2-13405  Hematopoietic Stem Cell Gene Therapy for Alpha
Thalassemia  
  Don Kohn, UCLA    $1,323,007  
    DISC2-13507  CAR T cells targeting abnormal N-glycans for the
treatment of refractory/metastatic solid cancers  
  Michael Demetriou, UC Irvine  $1,414,800  
  DISC2-13463  Drug Development of Inhibitors of Inflammation Using
Human iPSC-Derived Microglia (hiMG)  
  Stuart Lipton, Scripps Research Inst.  $1,658,123  
  DISC2-13390  Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure    Timothy Hoey, Tenaya Therapeutics  $1,215,000  
  DISC2-13417  AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder    Kyle Fink, UC Davis  $1,429,378  
  DISC2-13415  Defining the Optimal Gene Therapy Approach of
Human Hematopoietic Stem Cells for the Treatment of
Dedicator of Cytokinesis 8 (DOCK8) Deficiency  
  Caroline Kuo, UCLA  $1,386,232  
  DISC2-13498  Bioengineering human stem cell-derived beta cell
organoids to monitor cell health in real time and improve therapeutic outcomes in patients  
  Katy Digovich, Minutia, Inc.  $1,198,550  
  DISC2-13469  Novel antisense therapy to treat genetic forms of
neurodevelopmental disease.  
  Joseph Gleeson, UC San Diego  $1,180,654  
  DISC2-13428  Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)    Michael Bollong, Scripps Research Inst.  $1,244,160  
  DISC2-13456  Novel methods to eliminate cancer stem cells    Dinesh Rao, UCLA  $1,384,347  
  DISC2-13441  A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in
pediatric patients with Crohn’s diseas  
  Robert Barrett Cedars-Sinai  $776,340
  DISC2-13512  Modified RNA-Based Gene Therapy for Cardiac
Regeneration Through Cardiomyocyte Proliferation
  Deepak Srivastava, Gladstone Institutes  $1,565,784
  DISC2-13510  An hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly
neutralizing antibodies  
  Brian Lawson, The Scintillon Institute  $1,143,600  
  DISC2-13475  Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model    Xian-Jie Yang, UCLA  $1,345,691  

Can regenerative medicine turn back the clock on aging?

One of my favorite phrases is “standing room only”. I got a chance to use it last week when we held a panel discussion on whether regenerative medicine could turn back the clock on aging. The event was at the annual conference of the International Society for Stem Cell Research (ISSCR) and more than 150 people packed into a conference room to hear the debate (so far more than 800 also watched a live stream of the event.)

It’s not surprising the place was jammed. The speakers included:

  • Dr. Deepak Srivastava, the President of the Gladstone Institutes, an expert on heart disease and the former President of ISSCR.
  • Dr. Stanley “Tom” Carmichael, Chair of the Department of Neurology at UCLA and an expert on strokes and other forms of brain injury.
  • Adrienne Shapiro, the mother of a daughter with sickle cell disease, a tireless patient advocate and supporter of regenerative medicine research, and the co-founder of Axis Advocacy, a family support organization for people with sickle cell.
  • Jonathan Tomas, PhD, JD, the Chair of the CIRM Board.

And the topic is a timely one. It is estimated that as many as 90 percent of the people who die every day, die from diseases of aging such as heart disease, stroke, and cancer. So, what can be done to change that, to not just slow down or stop these diseases, but to turn back the clock, to repair the damage already done and replace cells and tissues already destroyed.

The conversation was enlightening, hopeful and encouraging, but also cautionary.

You can watch the whole event on our Youtube channel.

I think you are going to enjoy it.

Stem cells help researchers map out glaucoma in search for new treatments

Glaucoma is the world’s leading cause of irreversible blindness. There is no cure and current treatments are only able to slow down the progression of the disease. Now research using stem cells to create a genetic blueprint of glaucoma is giving scientist a powerful new tool to combat the disease.

Glaucoma occurs when healthy retinal ganglion cells, which relay information from the eyes to the brain, are damaged and die. However, researchers were unable to really understand what was happening because the only way to look at retinal ganglion cells was through very invasive procedures.

So, researchers in Australia took skin cells from people with glaucoma and people with healthy eyes and, using the iPSC method, turned them into retinal ganglion cells. They were then able to map the genetic expression of these cells and compare the healthy cells with the diseased ones.

In an interview with Science Daily, Professor Joseph Powell , who led the team, says they were able to identify more than 300 unique genetic features which could provide clues as to what is causing the vision loss.

“The sequencing identifies which genes are turned on in a cell, their level of activation and where they are turned on and off like a road network with traffic lights. This research gives us a genetic roadmap of glaucoma and identifies 312 sites in the genome where these lights are blinking. Understanding which of these traffic lights should be turned off or on will be the next step in developing new therapies to prevent glaucoma.”

Powell says by identifying underlying causes for glaucoma researchers may be able to develop new, more effective therapies.

The study is published in Cell Genomics.

Join us to hear how stem cell and gene therapy are taking on diseases of aging

It is estimated that as many as 90 percent of people in industrialized countries who die every day, die from diseases of aging such as heart disease, stroke, and cancer. Of those still alive the numbers aren’t much more reassuring. More than 80 percent of people over the age of 65 have a chronic medical condition, while 68 percent have two or more.

Current medications can help keep some of those conditions, such as high blood pressure, under control but regenerative medicine wants to do a lot more than that. We want to turn back the clock and restore function to damaged organs and tissues and limbs. That research is already underway and we are inviting you to a public event to hear all about that work and the promise it holds.

On June 16th from 3p – 4.30p PST we are holding a panel discussion exploring the impact of regenerative medicine on aging. We’ll hear from experts on heart disease and stroke; we will look at other ground breaking research into aging; and we’ll discuss the vital role patients and patient advocates play in helping advance this work.

The discussion is taking place in San Francisco at the annual conference of the International Society for Stem Cell Research. But you can watch it from the comfort of your own home. That’s because we are going to live stream the event.

Here’s where you can see the livestream: https://www.youtube.com/watch?v=CaUgsc5alDI

And if you have any questions you would like the panel to answer feel free to send them to us at info@cirm.ca.gov

Smoking marijuana could be bad for your heart, but there is an unusual remedy

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Smoking medical marijuana: Photo courtesy Elsa Olofsson

Millions of Americans use marijuana for medical reasons, such as reducing anxiety or helping ease the side effects of cancer therapy. Millions more turn to it for recreational reasons, saying it helps them relax. Now a new study says those who smoke marijuana regularly might be putting themselves at increased risk of heart disease and heart attack.

There has long been debate about the benefits versus the risks for using cannabis, with evidence on both sides to support each position. For example some studies have shown taking oral cannabinoids can help people cope with the nausea brought on by chemotherapy. Other studies have shown that regular use of marijuana can cause problems such as marijuana use disorder, a condition where the user is showing physical or psychological problems but has difficulty controlling or reducing their use of cannabis.

Now this latest study, from researchers at Stanford Medicine,  shows that THC, the psychoactive part of the drug, can cause inflammation in endothelial cells. These are the cells that line the interior of blood vessels. When these cells become inflamed it can cause a constriction of the vessels and reduce blood flow. Over time this can create conditions that increase the risk of heart disease and heart attack.

The researchers, led by Dr. Joe Wu, began by analyzing data from the UK Biobank. This included information about some 35,000 people who reported smoking marijuana. Of these around 11,000 smoked more than once a month. The researchers found that regular marijuana smokers:

  • Were significantly more likely than others to have a heart attack.
  • Were also more likely to have their first heart attack before the age of 50, increasing their risk of subsequent attacks.

The team then used the iPSC method to create human endothelial cells and, in the lab, found that THC appeared to promote inflammation in the cells. They also found signs it created early indications of atherosclerosis, where there is a buildup of fat and plaque in the arteries.

They then tested mice which had been bred to have high levels of cholesterol and who were given a high fat diet. Some of the mice were then injected with THC, at a level comparable to smoking one marijuana cigarette a day. Those mice had far larger amounts of atherosclerosis plaque in their arteries compared to the mice who didn’t get the THC.

In a news release, Dr.Wu, the lead author of the study, said: “There’s a growing public perception that marijuana is harmless or even beneficial. Marijuana clearly has important medicinal uses, but recreational users should think carefully about excessive use.”

On the bright side, the team also reported that the damage caused by THC can be stopped by genistein, a naturally occurring compound found in soy and fava beans. The study, in the journal Cell, also found that genistein blocked the bad impact of THC without impeding the good impacts.

“As more states legalize the recreational use of marijuana, users need to be aware that it could have cardiovascular side effects,” said Dr. Wu. “But genistein works quite well to mitigate marijuana-induced damage of the endothelial vessels without blocking the effects marijuana has on the central nervous system, and it could be a way for medical marijuana users to protect themselves from a cardiovascular standpoint.”

Study shows sleep deprivation impairs stem cells in the cornea 

We spend around one third of our life sleeping—or at least we should. Not getting enough sleep can have serious consequences on many aspects of our health and has been linked to high blood pressure, heart disease and stroke. 

A study by the American Sleep Apnea Association found that some 70 percent of Americans report getting too little sleep at least one night a month, and 11 percent report not enough sleep every night. Over time that can take a big toll on your mental and physical health. Now a new study says that impact can also put you at increased risk for eye disease.  

The study published in the journal Stem Cell Reports, looked at how sleep deprivation affects corneal stem cells. These cells are essential in replacing diseased or damaged cells in the cornea, the transparent tissue layer that covers and protects the eye.  

Researchers Wei Li, Zugou Liu and colleagues from Xiamen University, China and Harvard Medical School, USA, found that, in mice short-term sleep deprivation increased the rate at which stem cells in the cornea multiplied. Having too many new cells created vision problems.  

They also found that long-term sleep deprivation had an even bigger impact on the health of the cornea. Sleep-deprived mice had fewer active stem cells and so were not as effective in replacing damaged or dying cells. That in turn led to a thinning of the cornea and a loss of transparency in the remaining cells.  

The cornea— the transparent tissue layer covering the eye—is maintained by stem cells, which divide to replace dying cells and to repair small injuries.

The findings suggest that sleep deprivation negatively affects the stem cells in the cornea, possibly leading to vision impairment in the long run. It’s not clear if these findings also apply to people, but if they do, the implications could be enormous.  

The California Institute for Regenerative Medicine (CIRM) is also heavily involved in searching for treatments for diseases or conditions that affect vision. We have invested almost $150 million in funding 31 projects on vision loss including a clinical trial with UCLA’s Dr. Sophie Deng targeting the cornea, and other clinical trials for age-related macular degeneration and retinitis pigmentosa. 

Shared with permission from International Society for Stem Cell Research. Read the source release here

Stem cell-derived retinal patch continues to show promising results two years post-implantation

Earlier this year we wrote about the promising results of a phase 1 clinical trial aimed at replacing the deteriorating cells in the retinas of people suffering from age-related macular degeneration- one of the leading causes of blindness worldwide for people over 50. Now there’s even more good news! Highlighted in a news story on the UC Santa Barbara (UCSB) website, researchers are continuing to make progress in their bid to secure approval from the Food and Drug Administration for the life-changing treatment.

Through the collaborative efforts of researchers at UCSB, University of Southern California and California Institute of Technology, a stem cell-derived implant using cells from a healthy donor was developed. The bioengineered implant, described as a scaffold, was then implanted under the retina of 16 participants. If the implant was to work, the new cells would then take up the functions of the old ones, and slow down or prevent further deterioration. In the best-case scenario, they could restore some lost vision.

The first sets of trials, funded by the California Institute for Regenerative Medicine (CIRM), concentrated on establishing the safety of the patch and collecting data on its effectiveness. Parting ways with old practices, the participants in the trial were given just two months of immunosuppressants whereas in the past, using donor cells meant that patients often had to be given long-term immunosuppression to stop their body’s immune system attacking and destroying the implanted cells. The team found that after two years, the presence of the patch hadn’t triggered other conditions associated with implantation, such as the formation of new blood vessels or scar tissue that could cause a detachment of the retina.

Even more importantly, they found no sign of inflammation that indicated an immune response to the foreign cells even after the patient was taken off immunosuppressants two months post-implantation. “What really makes us excited is that there is some strong evidence to show that the cells are still there two years after implantation and they’re still functional,” said Mohamed Faynus, a graduate student researcher in the lab of stem cell biologist Dennis O. Clegg at UCSB.

Having passed the initial phase, the team of researchers now hopes to begin phase 2 of the trial. This time, they are aiming to more specifically assesses the effectiveness of the patch in participants. Looking even farther ahead, the Clegg Lab and colleagues are also exploring combining multiple cell types on the patch to treat patients at varying stages of the disease.

In addition, there have also been improvements made to extend the shelf life of the patch. “Cryopreservation of the therapy significantly extends the product’s shelf-life and allows us to ship the implant on demand all over the world, thus making it more accessible to patients across the globe,” said Britney Pennington, a research scientist in the Clegg Lab.

How a tiny patch is helping restore lasting vision

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Researchers are working on a stem cell-based retinal implant that could be used for people with with advanced dry age-related macular degeneration. (Photo/ Britney O. Pennington)

When Anna Kuehl began losing her vision, she feared losing the ability to read and go on long walks in nature—two of her favorite pastimes. Anna had been diagnosed with age-related macular degeneration, the leading cause of vision loss in the US. She lost the central vision in her left eye, which meant she could no longer make out people’s faces clearly, drive a car, or read the time on her watch.

Anna Kuehl

But a clinical trial funded by the California Institute for Regenerative Medicine  (CIRM) helped change that. And now, new data from that trial shows the treatment appears to be long lasting.

The treatment sprang out of research done by Dr. Mark Humayun and his team at USC. In collaboration with Regenerative Patch Technologies they developed a stem cell-derived implant using cells from a healthy donor. The implant was then placed under the retina in the back of the eye. The hope was those stem cells would then repair and replace damaged cells and restore some vision.

Dr. Mark Humayun, photo courtesy USC

In the past, using donor cells meant that patients often had to be given long-term immunosuppression to stop their body’s immune system attacking and destroying the patch. But in this trial, the patients were given just two months of immunosuppression, shortly before and after the implant procedure.

In a news story on the USC website, Dr. Humayun said this was an important advantage. “There’s been some debate on whether stem cells derived from a different, unrelated person would survive in the retina without long-term immunosuppression. For instance, if you were to receive a kidney transplant, long-term immunosuppression would be required to prevent organ rejection. This study indicates the cells on the retinal implant can survive for up to two years without long-term immunosuppression.”

Cells show staying power

When one of the patients in the clinical trial died from unrelated causes two years after getting the implant, the research team were able to show that even with only limited immunosuppression, there was no evidence that the patient’s body was rejecting the donor cells.

“These findings show the implant can improve visual function in some patients who were legally-blind before treatment and that the cells on the implant survive and remain functional for at least two years despite not being matched with those of the patient,” Humayun said.

For Anna Kuehl, the results have been remarkable. She was able to read an additional 17 letters on a standard eye chart. Even more importantly, she is able to read again, and able to walk and enjoy nature again.

Dr. Humayun says the study—published in the journal Stem Cell Reports—may have implications for treating other vision-destroying diseases. “This study addresses the debate over the viability of using mismatched stem cells — this shows that a mismatched stem cell derived implant can be safe and viable over multiple years.”

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

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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  

Researchers develop a stem cell-based implant for cartilage restoration and treating osteoarthritis

The Plurocart’s scaffold membrane seeded with stem cell-derived chondrocytes. Image courtesy of USC Photo/Denis Evseenko.

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Researchers at the Keck School of Medicine of USC have used a stem cell-based bio-implant to repair cartilage and delay joint degeneration in a large animal model. This paves the way to potentially treat humans with cartilage injuries and osteoarthritis, which occurs when the protective cartilage at the ends of the bones wears down over time. The disorder affects millions worldwide.

 The researchers are using this technology to manufacture the first 64 implants to be tested on humans with support from a $6 million grant from the California Institute for Regenerative Medicine (CIRM).

Researchers Dr. Denis Evseenko, and Dr. Frank Petrigliano led the development of the therapeutic bio-implant, called Plurocart. It’s composed of a scaffold membrane seeded with stem cell-derived chondrocytes, the cells responsible for producing and maintaining healthy articular cartilage tissue. 

In the study, the researchers implanted the Plurocart membrane into a pig model of osteoarthritis, resulting in the long-term repair of articular cartilage defects. Evseenko said the findings are significant because the implant fully integrated in the damaged articular cartilage tissue and survived for up to six months. “Previous studies have not been able to show survival of an implant for such a long time,” Evseenko added.

The researchers also found that the cartilage tissue generated was strong enough to withstand compression and elastic enough to accommodate movement without breaking.

Osteoarthritis, an often-painful disorder, can affect any joint, but most commonly affects those in our knees, hips, hands and spine. The USC researchers hope their implant will help prevent the development of arthritis and alleviate the need for invasive joint replacement surgeries.

“Many of the current options for cartilage injury are expensive, involve complex logistical planning, and often result in incomplete regeneration,” said Petrigliano. “Plurocart represents a practical, inexpensive, one-stage therapy that may be more effective in restoring damaged cartilage and improve the outcome of such procedures.”

Read the full study here and learn more about the CIRM grant here.