El bebé, Tobi recibió un tratamiento de células madre, financiado por el CIRM, mientras aún estaba en el útero.To read this blog in English, click here.
Michelle y Jeff se llenaron de felicidad cuando se enteraron de que iban a tener un bebé.
Luego, un examen de ultrasonido a las 20 semanas del embarazo reveló que el feto tenía espina bífida, una malformación congénita que ocurre cuando la columna vertebral y la médula espinal no se forman de manera adecuada. La espina bífida puede causar parálisis y otras complicaciones serias.
Se derivó a la pareja a un ensayo clínico en la Universidad de California, Davis, que lleva a cabo la Dra. Diana Farmer, cirujana fetal y neonatal reconocida a nivel internacional, y su colega, el Dr. Aijun Wang.
En este ensayo clínico, que se basó en una previa investigación financiada por el CIRM, se repara el defecto espinal aplicando células madre de una placenta donada, las cuales se insertan en una estructura sintética y se aplican al defecto de la médula espinal mientras el bebé se encuentra todavía en el útero.
El hijo de Michelle y Jeff, Tobi, fue el segundo paciente que recibió este tratamiento. Michelle dijo que la cirugía fue difícil, pero el nacimiento de su bebé valió la pena.
“Cuando lo abrazamos por primera vez dijimos, ‘No puedo creer que hayamos hecho esto. Lo logramos. Lo hicimos sin saber si funcionaría’.”
A los tres meses, el progreso de Tobi parece promisorio. Jeff y Michelle saben que pueden surgir problemas más adelante, pero por ahora se sienten agradecidos de haber formado parte de este ensayo.
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.
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.
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.
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:
Accelerate and de-risk pathways to commercialization for cell and gene therapies
Advance industry standards and incorporate quality-by-design in cell and gene therapy manufacturing, and
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.
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.
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.
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.
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.
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.
The 2022 Nobel Prize in Chemistry has been awarded to Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and K. Barry Sharpless of Scripps Research. The three scientists are recognized for their independent development and contributions to the field known as click chemistry and bioorthogonal chemistry.
Sharpless and Meldal are credited with laying the foundation for click chemistry, a functional form of chemistry in which molecular building blocks snap together quickly and efficiently. But it’s Bertozzi—a Stanford professor, chemist, mentor and early CIRM grantee—who is being recognized for taking click chemistry to a new dimension and utilizing it in living organisms.
A press release from The Royal Swedish Academy of Sciences describes Bertozzi’s accomplishments as follows:
“To map important but elusive biomolecules on the surface of cells – glycans – Bertozzi developed click reactions that work inside living organisms. Her bioorthogonal reactions take place without disrupting the normal chemistry of the cell.
These reactions are now used globally to explore cells and track biological processes. Using bioorthogonal reactions, researchers have improved the targeting of cancer pharmaceuticals, which are now being tested in clinical trials.”
Click chemistry and bioorthogonal reactions, the press release notes, have taken chemistry into the era of functionalism and brings the greatest benefit to humankind.
Bertozzi celebrates her Nobel Prize win. Image courtesy Kurt Hickman and Harry Gregory for Stanford.
As a recipient of a SEED Grant from the agency in 2007, Bertozzi helped jump-start human embryonic stem cell (hESC) research in California. Through that funding, Bertozzi’s lab at UC Berkeley studied the roles of cell surface sugars in the transformation of hESCs into cell types useful for the treatment of human diseases.
“This work will contribute to a better understanding of how stem cells interact with other cells in their environment and how they mature into different cell types,” Bertozzi said.
A Prolific Mentor
Bertozzi is also recognized as a prolific mentor, having advised more than 250 undergraduates, graduate students, and postdoctoral fellows, including CIRM Bridges alumni Ian Blong, whose experience working in Bertozzi’s lab was profiled in The Stem Cellar.
She also helped launched a program to prepare recent college graduates from diverse and historically underrepresented backgrounds to apply for doctorate programs in the sciences. In 2022, Bertozzi was recognized with a Lifetime Mentor Award from the American Association for the Advancement of Science for her commitment to mentorship and increasing diversity in science.
CIRM congratulates Bertozzi, Meldal and Sharpless on their Nobel Prize award and for their impressive accomplishments. Read an in-depth profile of Bertozzi and her work on the Stanford Magazine website. Read more about all three scientists and their work here. Read the news release from Stanford here.
Since then, we’ve expanded our mission to accelerate world class science for California and the world. We’ve funded and supported a pipeline of medical research from initial scientific discovery to development and testing. We also remain committed to training the next generation of regenerative medicine scientists to research cutting edge therapies for patients.
We’ve achieved a lot but recognize there’s still lots more work to be done. That’s why we’re inviting everyone to join us for a virtual webinar on October 12th for Stem Cell Awareness Day, a day when we mark the progress being made in regenerative medicine, stem cell and gene therapy research.
This Stem Cell Awareness Day, the CIRM team will highlight our achievements in research, clinical trials and education. We will also look ahead to explore how we can best further our mission.
Speakers will include: Jonathan Thomas — Chair, CIRM Board Dr. Kelly Shepard — Associate Director, Scientific Programs Dr. Lisa Kadyk — Associate Director, Therapeutics Development Dr. Mitra Hooshmand — Sr. Science Officer, Special Projects & Strategic Initiatives
The event is free and you can register here. If you have a question you would like to ask the team, please email them toinfo@cirm.ca.gov ahead of time. We will do our best to answer all questions during the webinar and those we can’t get to we’ll answer The Stem Cellar.
All her life, Madison Waterlander knew that she wanted to be a part of the medical field. But soon after graduating from the University of Hawaii with her undergraduate degree, the COVID-19 pandemic hit. It was during this time that she noticed how crucial biomedical research was in the medical field and lives of patients, and when she realized she had a passion for research.
She soon after found a master’s program in biotechnology and bioinformatics at California State University Channel Islands (CI), just a few minutes from Camarillo, the town she grew up in.
Looking further into the program, she learned that to pursue a Stem Cell Technology and Laboratory Management emphasis for the degree, she would have to complete a one-year lab internship funded by the California Institute for Regenerative Medicine (CIRM). The internship was part of CIRM’s Bridges to Stem Cell Research and Therapy Program, which prepares California undergraduate and master’s graduate students for highly productive careers in stem cell research and therapy development.
The opportunity to have hands-on experience in a lab through the internship solidified her decision to join the graduate program.
Once she settled into the program at CSU Channel Islands, she began her internship, which took place at UC Santa Barbara in the Weimbs Lab. While there, she researched the underlying mechanisms and possible new therapies for Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetic disorder characterized by the growth of numerous cysts in the kidneys.
“This CIRM-funded internship was so enriching for me, and I was able to expand my knowledge and skill set immensely in the laboratory,” Madison says. “I always knew that I loved science and the medical field, but this experience truly helped me realize that my strongest passion resides in the scientific research that goes into improving the quality of patient care and treatments.”
While Madison says the internship supported her knowledge in the lab and was an overall positive experience, she also faced some personal challenges during that time, including losing her grandma. She struggled with the loss, but Madison says her time in the lab allowed her to focus on something she loved doing and that her grandma always encouraged her to do.
“My grandma never would have wanted me to give up, so that truly helped to push me to continue on, and to try my hardest in every day to make an impact,” Madison says.
After a year of hard work in the lab, Madison officially graduated from CSU Channel Islands this summer with a Master of Science Degree in Biotechnology and Bioinformatics with a Stem Cell Technology and Laboratory Management emphasis. Now, Madison is pursuing a role in the biotechnology industry within translational biomedical research.
“I truly enjoyed every moment of my CIRM internship, and I feel that it truly revealed to me just how much I enjoy participating in biomedical research,” Madison says. “I’ve always felt that research feels like a treasure hunt looking for cures and treatments, so the more of us that are partaking in the treasure hunt, the quicker we can find new treatments and provide solutions for patients.”
Stories like Madison’s are why CIRM remains committed to training the next generation of scientists to conduct research and deliver regenerative medicine and stem cell therapies to patients. To date, there are 1,663 Bridges alumni, and another 109 Bridges trainees—including Madison—who are completing their internships in 2022.
The Stem Cellar 