As of this moment, there are over two million podcasts and over 48 million episodes to listen to on your favorite listening device. If you’re a true crime enthusiast like me, you’ve surely heard of Casefile or one of the other 94 podcasts on the topic. But what if you’re looking for something a little less ghastly and a little more uplifting?
The Stem Cell Podcast is an informative and entertaining resource for scientists and science enthusiasts (or really, anyone) interested in learning about the latest developments in stem cell research.
On their latest episode, dynamic co-hosts and research scientists Dr. Daylon James and Dr. Arun Sharma sit down with our President & CEO, Dr. Maria Millan, to discuss the impact of California’s culture of innovation on CIRM, the challenge of balancing hope vs. hype in the context of stem cell research/therapies, and the evolution of the agency over the past 15 years.
Listen on as Dr. Millan highlights some of CIRM’s greatest victories and shares our mission for the future.
About 10% of Americans suffer from knee osteoarthritis, a painful condition that can really impair mobility and quality of life. It’s often caused by an injury to cartilage, say when you were playing sports in high school or college, and over time it continues to degenerate and ultimately results in the loss of both cartilage and bone in the joint.
Current treatments involve either medication to control the pain or surgery. Medication works up to a point, but as the condition worsens it loses effectiveness. Knee replacement surgery can be effective, but is a serious, complicated procedure with a long recovery time. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to invest almost $6 million in an innovative stem cell therapy approach to helping restore articular cartilage in the knee.
Dr. Frank Petrigliano, Chief of the Epstein Family Center for Sports Medicine at Keck Medicine of the University of Southern California (USC), is using pluripotent stem cells to create chondrocytes (the cells responsible for cartilage formation) and then seeding those onto a scaffold. The scaffold is then surgically implanted at the site of damage in the knee. Based on scientific data, the seeded scaffold has the potential to regenerate the damaged cartilage, thus decreasing the likelihood of progression to knee osteoarthritis. In contrast to current methods, this new treatment could be an off-the-shelf approach that would be less costly, easier to administer, and might also reduce the likelihood of progression to osteoarthritis.
This is a late-stage pre-clinical program. The goals are to manufacture clinical grade product, carry out extensive studies to demonstrate safety of the approach, and then file an IND application with the FDA, requesting permission to test the product in a clinical trial in people.
“Damage to the cartilage in our knees can have a big impact on quality of life,” says Dr. Maria T. Millan, MD, President and CEO of CIRM. “It doesn’t just cause pain, it also creates problems carrying out simple, everyday activities such as walking, climbing stairs, bending, squatting and kneeling. Developing a way to repair or replace the damaged cartilage to prevent progression to knee osteoarthritis could make a major difference in the lives of millions of Americans. This program is a continuation of earlier stage work funded by CIRM at the Basic Biology and Translational stages, illustrating how CIRM supports scientific programs from early stages toward the clinic.”
Cancers of the blood, bone marrow and lymph nodes (also called hematologic malignancies) are the most common form of cancer in children and young adults. Current treatments can be effective but can also pose life-threatening health risks to the child. Now researchers at Stanford have developed a new approach and the Board of the California Institute for Regenerative Medicine (CIRM) voted to support that approach in a clinical trial.
The Board approved investing $11,996,634 in the study, which is the Stem Cell Agency’s 76th clinical trial.
The current standard of care for cancers such as acute leukemias and lymphomas is chemotherapy and a bone marrow (also called HSCT) transplant. However, without a perfectly matched donor the risk of the patient’s body rejecting the transplant is higher. Patients may also be at greater risk of graft vs host disease (GVHD), where the donor cells attack the patient’s body. In severe cases GVHD can be life-threatening.
Dr. Maria Grazia Roncarolo and her team at Stanford will test an immunotherapy cell approach using a therapy that is enriched with specialized immune cells called type 1 regulatory T (Tr1) cells. These cells will be infused into the patient following the bone marrow transplant. Both the Tr1 cells and the bone marrow will come from the same donor. The hope is this will help provide the patient’s immune system with these regulatory cells to combat life-threatening graft versus host disease and increase the success of treatment and bone marrow (HSCT) transplant.
“Every year around 500 children receive stem cell transplants in California, and while many children do well, too many experiences a rejection of the transplant or a relapse of the cancer,” says Dr. Maria T. Millan, President and CEO of CIRM. “Finding an improved therapy for these children means a shorter stay in the hospital, less risk of the need for a second transplant, and a greater quality of life for the child and the whole family.”
The CIRM Board has previously approved funding for 12 other clinical trials targeting cancers of the blood. You can read about them here.
Heart disease and stroke are two of the leading causes of death and disability and for people who have experienced either their treatment options are very limited. Current therapies focus on dealing with the immediate impact of the attack, but there is nothing to deal with the longer-term impact. The CIRM Board hopes to change that by funding promising work for both conditions.
Dr. Gary Steinberg and his team at Stanford were awarded almost $12 million to conduct a clinical trial to test a therapy for motor disabilities caused by chronic ischemic stroke. While “clot busting” therapies can treat strokes in their acute phase, immediately after they occur, these treatments can only be given within a few hours of the initial injury. There are no approved therapies to treat chronic stroke, the disabilities that remain in the months and years after the initial brain attack.
Dr. Steinberg will use embryonic stem cells that have been turned into neural stem cells (NSCs), a kind of stem cell that can form different cell types found in the brain. In a surgical procedure, the team will inject the NSCs directly into the brains of chronic stroke patients. While the ultimate goal of the therapy is to restore loss of movement in patients, this is just the first step in clinical trials for the therapy. This first-in-human trial will evaluate the therapy for safety and feasibility and look for signs that it is helping patients.
Another Stanford researcher, Dr. Crystal Mackall, was also awarded almost $12 million to conduct a clinical trial to test a treatment for children and young adults with glioma, a devastating, aggressive brain tumor that occurs primarily in children and young adults and originates in the brain. Such tumors are uniformly fatal and are the leading cause of childhood brain tumor-related death. Radiation therapy is a current treatment option, but it only extends survival by a few months.
Dr. Crystal Mackall and her team will modify a patient’s own T cells, an immune system cell that can destroy foreign or abnormal cells. The T cells will be modified with a protein called chimeric antigen receptor (CAR), which will give the newly created CAR-T cells the ability to identify and destroy the brain tumor cells. The CAR-T cells will be re-introduced back into patients and the therapy will be evaluated for safety and efficacy.
Stanford made it three in a row with the award of almost $7 million to Dr. Joe Wu to test a therapy for left-sided heart failure resulting from a heart attack. The major issue with this disease is that after a large number of heart muscle cells are killed or damaged by a heart attack, the adult heart has little ability to repair or replace these cells. Thus, rather than being able to replenish its supply of muscle cells, the heart forms a scar that can ultimately cause it to fail.
Dr. Wu will use human embryonic stem cells (hESCs) to generate cardiomyocytes (CM), a type of cell that makes up the heart muscle. The newly created hESC-CMs will then be administered to patients at the site of the heart muscle damage in a first-in-human trial. This initial trial will evaluate the safety and feasibility of the therapy, and the effect upon heart function will also be examined. The ultimate aim of this approach is to improve heart function for patients suffering from heart failure.
“We are pleased to add these clinical trials to CIRM’s portfolio,” says Maria T. Millan, M.D., President and CEO of CIRM. “Because of the reauthorization of CIRM under Proposition 14, we have now directly funded 75 clinical trials. The three grants approved bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures.”
One of the most amazing parts of an amazing job is getting to know the students who take part in CIRM’s SPARK (Summer Program to Accelerate Regenerative Medicine Knowledge) program. It’s an internship giving high school students, that reflect the diversity of California, a chance to work in a world-class stem cell research facility.
This year because of the pandemic I didn’t get a chance to meet them in person but reading the blogs they wrote about their experiences I feel as if I know them anyway.
The blogs were fun, creative, engaging and dealt with many issues, as well as stem cell and gene therapy research.
A common theme was how hard the students, many of whom knew little about stem cells before they started, had to work just to understand all the scientific jargon.
Areana Ramirez, who did her internship at UC Davis summed it up nicely when she wrote:
“Despite the struggles of taking over an hour to read a scientific article and researching what every other word meant, it was rewarding to know that all of the strain I had put on my brain was going toward a larger understanding of what it means to help others. I may not know everything about osteogenic differentiation or the polyamine pathway, but I do know the adversities that patients with Snyder-Robinson are facing and the work that is being done to help them. I do know how hard each one of our mentors are working to find new cures and are coming up with innovating ideas that will only help humankind.”
Lauren Ginn at City of Hope had the same experience, but said it taught her a valuable lesson:
“Make no mistake, searching for answers through research can sometimes feel like shooting arrows at a bulls-eye out of sight. Nonetheless, what CIRM SPARK has taught me is the potential for exploration that lies in the unknown. This internship showed me that there is so much more to science than the facts printed in textbooks.”
Rohan Upadhyay at UC Davis discovered that even when something doesn’t work out, you can still learn a lot:
“I asked my mentor (Gerhard Bauer) about what he thought had occurred. But unlike the textbooks there was no obvious answer. My mentor and I could only speculate what had occurred. It was at this point that I realized the true nature of research: every research project leads to more questions that need to be answered. As a result there is no endpoint to research. Instead there are only new beginnings.”
Melanie Nguyen, also at UC Davis, wrote her blog as a poem. But she saved the best part for the prose at the end:
“Like a hematopoietic stem cell, I have learned that I am able to pursue my different interests, to be multi-potential. One can indulge in the joys of biology while simultaneously live out their dreams of being an amateur poet. I choose it all. Similarly, a bone marrow stem cell can become whatever it may please—red, white, platelet. It’s ability to divide and differentiate is the source of its ingenuity. I view myself in the same light. Whether I can influence others with research, words, or stories, I know that with each route I will be able to make change in personalized ways.”
For Lizbeth Bonilla, at Stanford, her experiences transcended the personal and took on an even bigger significance:
“As a first-generation Mexican American, my family was thrilled about this internship and opportunity especially knowing it came from a prestigious institution. Unfortunately there is very little to no representation in our community in regards to the S.T.E.M. field. Our dreams of education and prosperity for the future have to be compromised because of the lack of support and resources. To maintain pride in our culture, we focus on work ethics and family, hoping it will be the next generations’ time to bring successful opportunities home. However, while this is a hope widely shared the effort to have it realized is often limited to men. A Latina woman’s success and interest in education are still celebrated, but not expected. As a first-generation Latina, I want to prove that I can have a career and hopefully contribute to raising the next leading generation, not with the hope that dreams are possible but to be living proof that they are.”
Reading the blogs it was sometimes easy to forget these are 16 and 17 year old students. They write with creativity, humor, thoughtfulness and maturity. They learned a lot about stem cell research over the summer. But I think they also learned a lot more about who they are as individuals and what they can achieve.
After almost 18 months – and counting – that have put us all to the test, made us wear masks, work from home, limit contact with all but the closest of family and friends it’s a wonderful thing to be able to get a glimpse of the future and feel that we are in good hands.
That’s how it felt this week when we held our SPARK conference. SPARK stands for Summer Program to Accelerate Regenerative Medicine Knowledge. The program helps high school students, that reflect the diversity of California, to take part in summer research at various institutions with a stem cell, gene therapy, or regenerative medicine focus.
We hope the experience will inspire these students to become the next generation of scientists. Many of the students are first generation Americans, many also come from families with limited resources and without our help might not be able to afford an internship like this.
As part of the program we ask the students to not only do stem cell research and prepare a poster of their work, we also ask them to blog about it. And the blogs they write are things of beauty.
It’s hard to pick winners from so many fine writers, but in the end a team of CIRMites managed to identify a few we thought really stood out. First was Hassan Samiullah who spent his internship at Cedars-Sinai. Hassan wrote three blogs charting his journey at the research facility, working with mice and a deadly brain cancer. This is part of one of his entries.
“When many of us think of scientists, we think of crazy people performing crazy procedures in a lab. While I won’t try refuting the first part, the crazy procedures can actually be very consequential to society at large. What is now common knowledge was once found in the discussion section of a research paper. The therapies we will use to treat cancer tomorrow are being tested in labs today, even if they’re being injected into mice brains.”
We liked his writing because he explained complex science clearly, with humor and obvious delight that he got to work in a research facility with “real” scientists. Crazy or otherwise. Here is his final blog which, I think, reflects the skill and creativity he brought to the task.
I’m almost at the end of my 7.5-week internship at Cedars-Sinai through the CIRM SPARK program. Looking back at the whole experience, I don’t think I’ve ever been through anything that’s required as much critical thinking.
I remember seeing pX330-dual-U6-Pten-Cdkn2a-Ex2-chimeric-BB-CBh-espCas9, and not having the slightest idea of what any of it meant. Sure, I understood the basics of what I was told: it’s a plasmid that can be transfected into mice brains to model glioblastoma tumors. But what do any of those strings of letters and numbers have to do with that? Well, I saw “Pten” and read it aloud: “P-t-e-n.” After I spelled it out like a kindergartener, I finally made a realization. p10 is a gene—specifically a tumor suppressor gene. I figured that the two jumbles of letters and numbers to the right must also be genes. Sure enough, the plasmid contains three mutated genes that get incorporated into a mouse’s genome, eventually leading to cancer. We didn’t actually end up using this model, however. Part of being in science is procedures not working out as expected.
Resilience is key.
When I found out that the image analysis software I was supposed to use didn’t support the type of data collection I needed to perform, I had to burn a little midnight oil to count the cells of interest manually. It proved to be well worth the effort: we found that mice tumors treated with radiation saw increased interactions between immune cells and endogenous (brain-resident) stem cells, even though they had fewer cells from the original tumor (difference wasn’t statistically significant due to an outlier in the control group). This is an important finding because it may explain the common narrative of glioblastoma: many patients see their tumors recede but suffer an aggressive relapse. This relapse may be due to immune cells’ interacting with stem cells to make them resistant to future treatments.
Understanding stem cells are so critical to cancer research, just as they are to many other fields of research. It is critical for everyone involved in science, medicine, healthcare, and policymaking to recognize and act on the potential of the regenerative medicine field to dramatically improve the quality of life for so many people.
This is just the beginning of my journey in science! I really look forward to seeing what’s next.
We look forward to it too Hassan.
Hassan wasn’t the only one we singled out for praise. Sheila Teker spent her summer at Children’s Hospital Oakland Research Institute. She says her internship didn’t get off to a very encouraging start.
“When the CHORI security guard implied that “kids aren’t allowed” on my first day–likely assuming I was a 10-year-old smuggling myself into a highly professional laboratory – I’d also personally doubted my presence there. Being 16, I wasn’t sure I’d fit in with others in such an intimidating environment; and never did I think, applying for this program, that I could be working with stem cells. I’d heard about stem cells in the news, science classes, and the like, but even doing any cell culturing at all seemed inaccessible to me. At my age, I’d become accustomed to and discouraged by rejection since I was perceived as “too young” for anything.”
Over the course of the summer Sheila showed that while you might question her age, no one should ever question her talent and determination.
Finally, we thought Alvin Cheng of Stanford also deserved recognition for his fine writing, starting with a really fun way to introduce his research into lower back pain.
“Perhaps a corpse would be reanimated”, Mary Shelley wrote her in 1831 edition of “Frankenstein”. Decades prior, Luigi Galvani discovered with his wife how a dead frog’s leg could twitch when an electric spark was induced. ‘Galvanism’ became the scientific basis behind the infamous novel and bioelectricity.”
While many of the students had to do their research remotely this year, that did not stop them doing amazing work. And working remotely might actually be good training for the future. CIRM’s Dr. Kelly Shepard, the Associate Director of Discovery and Translation and who runs the SPARK program, pointed out to the students that scientists now do research on the international space station from their labs here on earth, so the skills these SPARK students learned this past summer might prove invaluable in years to come.
Regardless of where they work, we see great things in the futures of these young scientists.
Anyone who knows anything about CIRM knows about Bob Klein. He’s the main author and driving force behind both Proposition 71 and Proposition 14, the voter-approved ballot initiatives that first created and then refunded CIRM. It’s safe to say that without Bob there’d be no CIRM.
Recently we had the great good fortune to sit down with Bob to chat about the challenges of getting a proposition on the ballot in a time of pandemic and electoral pandemonium, what he thinks CIRM’s biggest achievements are (so far) and what his future plans are.
Recently the CIRM Board voted to support the creation of a Rare Disease Advisory Council (RDAC) in California. An RDAC is an advisory body providing a platform for the rare community to have a stronger voice in state government. They address the needs of rare patients and families by giving stakeholders an opportunity to make recommendations to state leaders on critical issues including the need for increased awareness, diagnostic tools and access to affordable treatments and cures.
California is now in the process of creating an RDAC but, as a recent article in STAT highlighted, we are far from the only one.
21 states give rare disease patients a seat at the table. The other 29 need to follow suit By Guadalupe Hayes-Mota Originally published by STAT on July 26, 2021
A powerful movement is taking shape in the U.S. rare disease community that could transform the lives of millions of people. That’s right — millions. Even though a single rare disease may affect only a few individuals, there are several thousand of these problematic diseases that are difficult to identify and treat.
Since 2015, 21 U.S. states have passed legislation to create Rare Disease Advisory Councils that provide platforms for patients and family members to communicate with experts, policymakers, and the broader public. It’s critical to seize this hopeful moment because the needs of so many people living with rare diseases go unaddressed.
I know because I’m one of them.
I was born and raised in a small town in Mexico and diagnosed at birth with hemophilia, a rare genetic disease that prevents the blood from clotting after trauma or injury. While treatment existed in other parts of the world, I had only limited access to it, forcing me to live an isolated childhood indoors, protected and isolated from the world.
When my appendix burst at age 12, I underwent emergency surgery, followed by a desperate eight-hour ambulance ride to a hospital in another town in search of better medication to stop the bleeding. Doctors told my parents I was unlikely to survive, but against all odds I did — after clinically dying twice in the operating room. I am one of the few lucky people with my condition to have survived severe bleeding events without treatment.
After this traumatic incident, my family moved to a small town in California’s Mojave Desert. Navigating the health care system as an immigrant and not knowing the language was complicated. Accessing treatment and services for my disease was almost impossible at first. The nearest specialist was 90 minutes away. Thankfully, with help from the hemophilia association chapter in our area, I gained access to care and treatment.
Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $8.39 million to the University of California, San Francisco (UCSF) to fund a clinical trial for sickle cell disease (SCD). An additional $51.08 million was awarded to fifteen community colleges and universities across California to fund undergraduate and master’s level programs that will help train the next generation of stem cell researchers.
SCD is an inherited blood disorder caused by a single gene mutation that changes a single base in the B globin gene leading to the production of defective hemoglobin that polymerizes and damages red blood cells thus the “sickle” shaped red blood cells. The damaged cells cause blood vessels to occlude/close up and that can lead to multiple organ damage as well as reduced quality of life and life expectancy.
Mark Walters, M.D., and his team at UCSF Benioff Children’s Hospital Oakland will be conducting a clinical trial that uses CRISPR-Cas9 gene editing technology to correct the genetic mutation in the blood stem cells of patients with severe SCD. The corrected blood stem cells will then be reintroduced back into patients with the goal of correcting the defective hemoglobin and thus producing functional, normal shaped red blood cells.
This clinical trial will be eligible for co-funding under the landmark agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI) of the NIH. The CIRM-NHLBI agreement is intended to co-fund cell and gene therapy programs under the NHLBI’s “Cure Sickle Cell” initiative. The goal is to markedly accelerate the development of cell and gene therapies for SCD. CIRM has previously funded the preclinical development of this therapy through a Translational award as well as its IND-enabling studies through a Late Stage Preclinical award in partnership with NHLBI.
The CIRM Bridges to Stem Cell Research and Therapy program provides undergraduate and master’s students with the opportunity to take stem cell related courses and receive hands on experience and training in a stem cell research related laboratory at a university or biotechnology company. Fifteen institutions received a total of $51.08 million to carry out these programs to train the next generation of scientists.
The awards are summarized in the table below.
Bridges to Stem Cell Research and Therapy at Pasadena City College
Pasadena City College
CIRM Bridges to Stem Cell Research and Therapy Training Grant
CSU San Marcos
Bridges to Stem Cell Research Internship Program
San Diego State University
CIRM Bridges 3.0
CIRM Regenerative Medicine and Stem Cell Research Biotechnology Training Program
CSU Long Beach
Stem Cell Internships in Laboratory-based Learning (SCILL) continue to expand the scientific workforce for stem cells research and therapies.
San Jose State University
Strengthening the Pipeline of Master’s-level Scientific and Laboratory Personnel in Stem Cell Research
CIRM Bridges Science Master’s Program
San Francisco State University
CIRM Graduate Student Training in Stem Cell Sciences in the Stem Cell Technology and Lab Management Emphasis of the MS Biotechnology Program
CSU Channel Islands
CSUN CIRM Bridges 3.0 Stem Cell Research & Therapy Training Program
Stem Cell Scholars: a workforce development pipeline, educating, training and engaging students from basic research to clinical translation.
CSU San Bernardino
Training Master’s Students to Advance the Regenerative Medicine Field
Cal Poly San Luis Obispo
Building Career Pathways into Stem Cell Research and Therapy Development
City College of San Francisco
Bridges to Stem Cell Research and Therapy: A Talent Development Program for Training Diverse Undergraduates for Careers in Regenerative Medicine
CIRM Bridges to Stem Cell Research and Therapy
Berkeley City College
“We are pleased to fund a promising trial for sickle cell disease that uses the Nobel Prize winning gene editing technology CRISPR-Cas9,” says Maria T. Millan, M.D., President and CEO of CIRM. “This clinical trial is a testament to how the CIRM model supports promising early-stage research, accelerates it through translational development, and advances it into the clinics. As the field advances, we must also meet the demand for promising young scientists. The CIRM Bridges programs across the state of California will provide students with the tools and resources to begin their careers in regenerative medicine.”
At first glance Lauren Miller Rogen and Dr. David Higgins seem an unlikely pair. She’s an actor, writer, director and has worked with some of the biggest names in Hollywood. He has a doctorate in molecular biology and genetics and has worked at some of the most well-known companies in biotech. But together they make a great team.
Lauren and David are both on the CIRM Board. She’s a patient advocate for Alzheimer’s and the driving force (with her husband Seth) of HFC (Hilarity for Charity), which has raised millions of dollars to help families battling the disease and to educate young people about the condition. It’s also made a lot of people laugh along the way. David is a patient advocate for Parkinson’s and has been instrumental is creating support groups that help patients and families cope with the disease.