CIRM

The Most Read Stem Cellar Blog Posts of 2022

/ Esteban Cortez / Leave a comment

This year was a momentous one for the California Institute for Regenerative Medicine (CIRM). You can read some of our achievements in our 2021-2022 annual report.  

As always, we shared our most exciting updates and newsworthy stories—topics ranging from stem cell research to diversity in science—right here on The Stem Cellar. More than 100,000 blog visitors followed along throughout the year!  

In case you missed them, here’s a recap of our most popular blogs of 2022. We look forward to covering even more topics in 2023 and send a sincere thank you to our wonderful Stem Cellar readers for tuning in!   

In Memory of Kevin McCormack 

We cannot close out the year without honoring our dear friend and colleague Kevin McCormack, who passed away suddenly in December. Kevin was CIRM’s Director of Patient Advocacy and loved writing for The Stem Cellar. He did a wonderful job in translating complex science for the general public and was a great mentor to the CIRM team. Many of his closest friends and colleagues wrote memories about him, and we compiled them in this blog post honoring his life and dedication to CIRM and patients everywhere.  

How stem cells helped Veronica fight retinitis pigmentosa and regain her vision 

We shared the story of Veronica McDougall, who thought everyone saw the world the way she did: blurry, slightly out-of-focus and with tunnel vision. When she was 24, she went to see a specialist who told her she had retinitis pigmentosa, a rare degenerative condition that would eventually leave her legally blind. Click through to read about her experience participating in a CIRM-funded clinical trial with a company called jCyte. 

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

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. Check out this blog to learn how a team at Stanford Medicine used the iPSC method to create human endothelial cells and, in the lab, found that THC appeared to promote inflammation in the cells. 

A pioneering couple uproot their lives to help their baby 

This year, we shared some encouraging news about a CIRM-funded stem cell clinical trial for spina bifida at UC Davis Health. Spina bifida is a birth defect that occurs when the spine and spinal cord don’t form properly and can result in life-long walking and mobility problems for the child, even paralysis. This blog told the story of parents Michelle Johnson and Jeff Maginnis, who learned 20 weeks into the pregnancy that the fetus had spina bifida. Read the whole story to learn about their experience and the status of their baby Tobi.  

And that wraps up The Stem Cellar’s top blog posts of 2022! If you’re looking for more ways to get the latest updates from The Stem Cellar and CIRM, follow us on social media on Facebook, Twitter, LinkedIn, and Instagram.

Three women with ties to CIRM featured in 2022 Women in Biopharma list 

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Endpoints News released its 2022 Women in Biopharma list, which recognizes 20 of the top women leading biopharma research and development (R&D).  

This year, the publication received more than 500 entries and selected 20 women “who have blazed trails and are still promising to reshape biopharma R&D for years to come.” 

There are many amazing finalists featured this year, but three in particular stood out for their ties to the California Institute for Regenerative Medicine (CIRM). Those three are:  

Jennifer Gordon, Ph.D. — Senior Vice President of Research and Development at Excision BioTherapeutics 

Dr. Jennifer Gordon and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. CIRM is funding a clinical trial to test EBT-101 in patients with HIV. 

This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe.  

The goal of the treatment is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured. 

Barbara Wirostko — Co-founder and CMO at Qlaris Bio 

Barbara Wirostko is the co-founder and CMO at Qlaris Bio, a clinical stage biotech company committed to developing therapies for patients suffering from serious and debilitating ophthalmic diseases.  

In addition to her work there, Barbara is a member of CIRM’s Grants Working Group (GWG), which is responsible for evaluating the scientific merit of all applications submitted to CIRM and provides funding recommendations to the CIRM board.  

In the Endpoints News profile, Wirostko shares that she was inspired by her father, also an ophthalmologist, and his desire to help people. 

“I think that was the other thing that really drew me to ophthalmology — is that you were able to work with patients, make a difference in people’s lives, also have a surgical as well as a medical aspect, practicing medicine, and then also have a family,” she said. 

Dr. Lili Yang – UCLA associate professor, Co-founder of Appia Bio and Immune Design 

We’ve written about Dr. Lili Yang’s work on the Stem Cellar blog.  

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

With support from several CIRM grants, Dr. Yang has developed a platform that can use healthy donor blood stem cells to produce clinical scalable “off-the-shelf” iNKT cells. That has led to the creation of start-up company Appia Bio, and talks with the FDA about testing a series of iNKT cell products in clinical trials. 

“I have this dream that cell therapy can become off-the-shelf, and how this would really help all cancer patients in need. The current cancer cell therapy requires treating patients one-by-one, resulting in a steep price that is hard to afford,” Dr. Yang says.  

“Not everyone lives near a hospital capable of handling such a personalized therapy or can afford such a steep price. If we can make this therapy with centralized manufacturing, pre-quality controlled and ready for wide use then we don’t need to worry about the gender or age or location of the patient.” 

CIRM congratulates all the extraordinary women featured in the Endpoints News 2022 Women in Biopharma list. To see all the finalists, read the official announcement here or visit the Endpoints News website.  

Reasons to be thankful this Thanksgiving: creative nerds

/ Kevin McCormack / Leave a comment

We at the California Institute for Regenerative Medicine have a lot to be thankful for this Thanksgiving. We get to work with some extraordinary colleagues, we get to know some remarkable patient advocates who are pioneers in volunteering for stem cell and gene therapies, and we have a front row seat in a movement that is changing the face of medicine.

We also get to work with some brilliant scientists and help support their research. As if we needed any reminders of how important that funding is, we thought we would share this video with you. It’s from the talented post docs and researchers at the University of California San Diego. It’s a delightful parody of the Cyndi Lauper classic “Girls Just Wanna Have Fun”. Only in this case it’s “Nerds Just Wanna Have Funds.”

Enjoy, and Happy Thanksgiving.

Study could pave the way in reducing decline in muscle strength as people age 

/ Esteban Cortez / Leave a comment

A study by Stanford Medicine researchers in older mice may lead to treatments that help seniors regain muscle strength lost to aging.

Muscle stem cells—which are activated in response to muscle injury to regenerate damaged muscle tissue—lose their potency with age. A study from the National Health and Nutrition Examination Survey showed that five percent of adults aged 60 and over had weak muscle strength, and thirteen percent had intermediate muscle strength. 

Now, researchers at Stanford Medicine are seeing that old mice regain the leg muscle strength of younger animals after receiving an antibody treatment that targets a pathway mediated by a molecule called CD47.  

The study was published in Cell Stem Cell and is co-funded by the California Institute for Regenerative Medicine (CIRM).  

A Closer Look at CD47 

CD47 is a protein found on the surface of many cells in the body. Billed as the “don’t eat me” molecule, it is better known as a target for cancer immunotherapy. It’s common on the surface of many cancer cells and protects them from immune cells that patrol the body looking for dysfunctional or abnormal cells.  

Stanford researchers are finding that old muscle stem cells may use a similar approach to avoid being targeted by the immune system. 

It’s been difficult to determine why muscle stem cells lose their ability to divide rapidly in response to injury or exercise as they age. Dr. Ermelinda Porpiglia, the lead author of the study, used a technique called “single-cell mass cytometry” to study mouse muscle stem cells.  

Using the technique, Porpiglia focused on CD47, and found that the molecule was found at high levels on the surface of some muscle stem cells in older mice, but at lower levels in younger animals. Porpiglia also found that high levels of CD47 on the surface of muscle stem cells correlate with a decrease in their function.   

“This finding was unexpected because we primarily think of CD47 as an immune regulator,” Porpiglia said. “But it makes sense that, much like cancer cells, aged stem cells might be using CD47 to escape the immune system.” 

Testing an Antibody 

Further investigation revealed that a molecule called thrombospondin, which binds to CD47 on the surface of the muscle stem cells, suppresses the muscle stem cells’ activity.  

Porpiglia showed that an antibody that recognizes thrombospondin and blocks its ability to bind to CD47 dramatically affected the function of muscle stem cells. Cells from older animals divided more robustly when growing in a laboratory dish in the presence of the antibody, and when the antibody was injected into the leg muscles of old mice the animals developed bigger and stronger leg muscles than control animals.  

When given prior to injury, the antibody helped the aged animals recover in ways similar to younger mice. 

Porpiglia said, “We are hopeful that it might one day be possible to inject an antibody to thrombospondin at specific sites in the body to regenerate muscle in older people or to counteract functional problems due to disease or surgery.” 

These results are significant because they could one day make it possible to boost muscle recovery in humans after surgery and reduce the decline in muscle strength as people age, but researchers say more work is needed.  

“Rejuvenating the muscle stem cell population in older mice led to a significant increase in strength,” said Dr. Helen Blau, a senior author of the study. “This is a localized treatment that could be useful in many clinical settings, although more work needs to be done to determine whether this approach will be safe and effective in humans.” 

CIRM has previously funded work with researchers using CD47 that led to clinical trials targeting cancer. You can read about that work here and here. That work led to the creation of a company, Forty Seven Inc, which was eventually bought by Gilead for $4.9 billion.  

Read the original release by Krista Conger on the Stanford Medicine website. 

Sweet 16 and counting for stem cell clinical trial

/ Kevin McCormack / 1 Comment

Dr. Judy Shizuru: Photo courtesy Jasper Therapeutics

Over the years the California Institute for Regenerative Medicine (CIRM) has invested a lot in helping children born with severe combined immunodeficiency (SCID), a fatal immune disorder. And we have seen great results with some researchers reporting a 95 percent success rate in curing these children.

Now there’s more encouraging news from a CIRM-funded clinical trial with Jasper Therapeutics. They have announced that they have tested their approach in 16 patients, with encouraging results and no serious adverse events.

Let’s back up a little. Children born with SCID have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life. Several of the approaches CIRM has funded use the child’s own blood stem cells to help fix the problem. But at Jasper Therapeutics they are using another approach. They use a bone marrow or hematopoietic stem cell transplant (HCT).   This replaces the child’s own blood supply with one that is free of the SCID mutation, which helps restore their immune system.

However, there’s a problem. Most bone marrow transplants use chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. It can be effective, but it is also toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

To get around that problem Jasper Therapeutics is using an antibody called JSP191 – developed with CIRM funding – that directs the patient’s own immune cells to kill diseased blood stem cells, creating room to transplant new, healthy cells. To date the therapy has already been tested in 16 SCID patients.

In addition to treating 16 patients treated without any apparent problems,  Jasper has also been granted Fast Track Designation by the US Food and Drug Administration. This can help speed up the review of treatments that target serious unmet conditions. They’ve also been granted both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.

In a news release, Ronald Martell, President and CEO of Jasper Therapeutics said:

“The FDA’s Fast Track designation granted for JSP191 in Severe Combined Immunodeficiency (SCID) reinforces the large unmet medical need for patients with this serious disease. Along with its previous designations of Orphan and Rare Pediatric Disease for JSP191, the FDA’s Fast Track recognizes JSP191’s potential role in improving clinical outcomes for SCID patients, many of whom are too fragile to tolerate the toxic chemotherapy doses typically used in a transplant.”

Apply Now for New Manufacturing Funding Opportunity

/ Esteban Cortez / Leave a comment

The California Institute for Regenerative Medicine (CIRM) has set goals through its five-year strategic plan to continue to deliver the full potential of regenerative medicine to the people of California and around the world. 

One of those goals is to overcome manufacturing hurdles for the delivery of regenerative medicine therapies by building a public-private manufacturing partnership network. 

This is essential because the field needs to create standardized manufacturing processes to transition from the production of smaller batches of therapies for use in clinical trials, to the larger batches required by full-scale commercialization. The manufacturing process for cell and gene therapies is more complex than for other biologics, so CIRM is committed to creating a network to overcome those challenges.

In working towards that goal, CIRM is pleased to announce a new funding opportunity within our Infrastructure Program, the INFR5 Cell and Gene Therapy Manufacturing Network (Phase 1) Awards.  
 
The California Cell and Gene Therapy Manufacturing Network aims to establish a statewide manufacturing network comprising academic process development and GMP manufacturing facilities as well as industry manufacturing partners that will: 

  1. Accelerate and de-risk pathways to commercialization for cell and gene therapies 
  1. Advance industry standards and incorporate quality-by-design in cell and gene therapy manufacturing, and 
  1. Build a diverse, highly skilled manufacturing workforce in California. 

CIRM will issue two phases of awards governed by two separate requests for applications (RFAs). This RFA describes the first phase of awards that will fund California academic cell and gene therapy GMP manufacturing facilities to make initial progress toward the three network goals (described above) at their individual facilities. 

To apply for this award, please visit our website to download the Program Announcement and access a link to the application.  

Update: If you’re interested in learning more about the INFR5 Phase 1 Awards, eligibility requirements, the application and review process, and more, the CIRM team hosted an informational webinar in November. Watch a video recording of the webinar here. The slide deck is available here.

How this scientist changed paths to become a stem cell researcher

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Aaliyah Staples-West didn’t originally envision becoming a stem cell researcher. As a student at San Diego State University, she admits that she sometimes struggled with reading protocols or finishing experiments on time. She also was originally studying chemistry, a very distinct scientific field from regenerative medicine. 

But when she saw a post on Instagram about the California Institute for Regenerative Medicine (CIRM) Bridges to Stem Cell Research and Therapy internship program, she did a bit of research about it and ultimately stepped up to pursue the opportunity.   

“Everything I was looking for aligned with what I wanted to do,” she says. “I applied and I was greeted with open arms to an acceptance about a week later.” She even stayed in college for an extra semester so she could enroll in the CIRM internship program.

During the year-long internship—which took place at UC San Diego in the Sanford Consortium for Regenerative Medicine—Aaliyah studied and modeled a rare disease called Cockayne Syndrome B (CSB). CSB is a rare disease which causes short stature, premature aging, severe photosensitivity, and moderate to severe learning delay. 

In the lab, Aaliyah worked with stem cells to derive brain organoids, which are three-dimensional, organ-like clusters of cells. She also researched vascular endothelial cells, which form a single cell layer that lines all blood vessels. She tested and observed these to further understand the causes of CSB.  

Aaliyah also had opportunities to do work outside of the lab, traveling to various scientific conferences across the state to explain her work to other scientists.

She enjoyed sharing her findings, but Aaliyah says it was a challenge at first to learn all the complex science and terminology relating to stem cells. She overcame that obstacle by asking lots of questions and putting in extra effort to understanding the biology and reasoning behind her work.  

“I would write down all the terms my mentor would say that I didn’t understand and look them up,” she says. “I would even practice using them in a sentence. I made it very intentional that if I wanted to continue researching in this field I needed to be on the same page.”

Aaliyah and her Bridges cohort at the CIRM Bridges conference in San Diego.

Now that her internship is over, Aaliyah is much more confident and has learned various techniques to successfully complete research projects. She now works for biotechnology company Resilience as a research associate working with induced pluripotent stem cells (iPSCs) and hematopoietic stem cells. Though she originally intended to go to medical school, she is now looking into MD/PhD programs where she can apply all that she’s learned in her training and education.  

“I never thought I would have a love for stem cell research until participating in this program,” she says. “Stem cell research and regenerative medicine provide infinite opportunities for developing, understanding and potentially curing diseases. It’s important to continue this type of research to ensure science is quickly evolving and to make an impact on overall health.” 

To date, there are 1,663 Bridges alumni, and another 109 Bridges trainees are completing their internships in 2022.  Learn more about CIRM’s internship programs here. 

All photos courtesy of Sarah White/SDSU and Aaliyah Staples-West.

CIRM President & CEO Dr. Maria Millan recognized as one of the most influential women in Bay Area business

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Dr. Maria Millan has been recognized by the San Francisco Business Times as one of the most influential women in Bay Area business for her work leading the California Institute for Regenerative Medicine (CIRM), California’s stem cell and regenerative medicine agency.  

Under her leadership, CIRM has generated a robust and growing portfolio as a patient-centric funder, partner, accelerator, and de-risker for over 1,000 projects in basic, translational, and clinical research, as well as infrastructure and education programs. 

In addition to highlighting her achievements at CIRM, Dr. Millan also shared some of her personal background with the publication.  

“I immigrated to the U.S. from the Philippines at 6 years old with my younger siblings one year after my mother, accompanied by my father, was recruited as a nurse to New York City,” she said. “I honed down my English watching ‘Sesame Street’ and the ‘Electric Company.’” 

When asked about the biggest obstacle facing women leaders, Dr. Millan said, “Work-life balance, learning that ‘good’ is enough in certain circumstances to achieve ‘great,’ and embracing what makes us unique — our experiences as women and as mothers and to leveraging those skills to leadership roles.” 

Congratulations to Dr. Millan and this year’s winners! To see the full list of award recipients, click here.  

Apply by Nov. 8th for CIRM Discovery stage funding!

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The California Institute for Regenerative Medicine (CIRM) is pleased to announce a new opportunity within our current funding cycle for Discovery stage programs: the DISC0 Foundation Awards which focus on foundational and/or mechanistic research projects grounded in human biology and/or disease pathology.  
  
Projects funded through the Foundation Awards should propose impactful or innovative research that culminates in a discovery or technology that would:  

  • Advance our understanding of the biology of stem or progenitor cells that is relevant to human biology and disease; or   
  • Advance the application of genetic research that is relevant to human biology and disease and pertains to stem cells or regenerative medicine; or  
  • Advance the development or use of human stem cells as tools for biomedical innovation; or   
  • Lead to the greater applicability of regenerative medicine discoveries to communities representing the full spectrum of diversity.  

CIRM’s goal is that the outcomes of the projects derived from this opportunity will ultimately create new avenues and provide a rigorous foundation for translational and clinical development work.   
 
Since Proposition 14 dedicates more than a quarter of funds to support research and development of treatments for diseases and conditions of the brain and central nervous system (CNS), CIRM encourages the submission of proposals focused on increasing our understanding of the fundamental biology of CNS disorders.  
 
Please visit our website to download the DISC0 Program Announcement and read about program requirements before submitting your application. Applications are due November 8th, 2022 by 2:00 PM PST.   

The CIRM Science team recently hosted a webinar addressing DISC0 eligibility requirements, the application and review process, and how this program fits into CIRM’s overall Strategic Plan and Mission. The webinar includes a half-hour presentation by CIRM staff followed by a half-hour for Q&A. You can view the webinar below or direct any questions about the program and applications to discovery@cirm.ca.gov.

We look forward to your applications! 

CIRM-funding supports world’s first stem cell treatment for spina bifida delivered during fetal surgery

/ Esteban Cortez / 2 Comments
Dr. Diana Farmer (right) meets with Emily Lofton and her baby Robbie who had stem cell treatment for spina bifida in the womb. Photo: UC Davis Health

The California Institute for Regenerative Medicine (CIRM) recently shared some encouraging news on The Stem Cellar about a CIRM-funded stem cell clinical trial for spina bifida at UC Davis Health. 
 
Spina bifida is a birth defect that occurs when the spine and spinal cord don’t form properly and can result in life-long walking and mobility problems for the child, even paralysis. 
 
Now, UC Davis has released more details about the clinical trial and the babies born after receiving the world’s first spina bifida treatment combining surgery with stem cells. The story was featured in BBC News and The Sacramento Bee.  
 
The first phase of the trial is funded by a $9 million grant from the California Institute for Regenerative Medicine. 
 
The one-of-a-kind treatment, delivered while a fetus is still developing in the mother’s womb, could improve outcomes for children with this birth defect. 

A Decade’s Work

“I’ve been working toward this day for almost 25 years now,” said Dr. Diana Farmer, the world’s first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.  

In previous clinical trial, Farmer had helped to prove that fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.  

Dr. Diana Farmer and Dr. Aijun Wang. Photo courtesy UC Davis Health

Farmer recruited bioengineer Dr. Aijun Wang to help take that work to the next level. Together, they researched and tested ways to use stem cells and bioengineering to advance the effectiveness and outcomes of the surgery.  

Farmer, Wang and their research team have been working on their novel approach using stem cells in fetal surgery for more than 10 years. Over that time, animal modeling has shown it is capable of preventing the paralysis associated with spina bifida. 

Preliminary work by Farmer and Wang proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells, held in place with a biomaterial scaffold to form a “patch,” helped lambs with spina bifida walk without noticeable disability. When the team refined their surgery and stem cells technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida. 

The CuRe Trial

When Emily and her husband Harry learned that they would be first-time parents, they never expected any pregnancy complications. But the day that Emily learned that her developing child had spina bifida was also the day she first heard about the CuRe trial, as the clinical trial is known.  

Participating in the trial would mean that she would need to temporarily move to Sacramento for the fetal surgery and then for weekly follow-up visits during her pregnancy.  

After screenings, MRI scans and interviews, Emily received the news that she was accepted into the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.  

Farmer and Wang’s team manufactured clinical grade stem cells—mesenchymal stem cells—from placental tissue in the UC Davis Health’s CIRM-funded Institute for Regenerative Cures. The lab is a Good Manufacturing Practice (GMP) Laboratory for safe use in humans. It is here that they made the stem cell patch for Emily’s fetal surgery. 

The Procedure

During Emily’s historic procedure, a small opening was made in her uterus and they floated the fetus up to that incision point so they could expose its spine and the spina bifida defect. 

Credit: UC Davis Health

Then, the stem cell patch was placed directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate. The team declared the first-of-its-kind surgery a success. 

On Sept. 20, 2021, at 35 weeks and five days gestation, Robbie was born at 5 pounds, 10 ounces, 19 inches long via C-section. 

For Farmer, this day is what she had long hoped for, and it came with surprises. If Robbie had remained untreated, she was expected to be born with leg paralysis. 

Baby Robbie underwent treatment for spina bifida while in the womb. Photo credit: UC David Health

“It was very clear the minute she was born that she was kicking her legs and I remember very clearly saying, ‘Oh my God, I think she’s wiggling her toes!’” said Farmer. “It was amazing. We kept saying, ‘Am I seeing that? Is that real?’” 

Both mom and baby are at home and in good health. Robbie just celebrated her first birthday. 

Emily Lofton and her baby daughter Robbie who underwent treatment for spina bifida while in the womb.

The CuRe team is cautious about drawing conclusions and says a lot is still to be learned during this safety phase of the trial. The team will continue to monitor Robbie and the other babies in the trial until they are 6 years old, with a key checkup happening at 30 months to see if they are walking and potty training. 

“This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come,” Emily said. “We are honored to be part of history in the making.” 

Read the official release from UC Davis Health here.