It’s nice to be appreciated

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Photo: courtesy City of Hope

No one likes to be taken for granted, to feel that people only like you because you have scads of cash and they want some of it. That’s why it’s so lovely when you feel you are appreciated because of all the things money makes possible.

That’s how it felt when we saw City of Hope’s news release about our funding to train the next generation of scientists and leaders in the field of regenerative medicine. CIRM has awarded COH $4.86 million as part of its Research Training Program in Stem Cell Biology and Regenerative Medicine.

The program provides stem cell and gene therapy research training for up to 6 graduate students and 12 postdocs at the Beckman Research Institute of City of Hope. In addition to 3 years of research, the training includes coursework, patient engagement and community outreach activities.

In a news release, Dr. Nadia Carlesso, chair of the Department of Stem Cell Biology and Regenerative Medicine, said this funding is important in training a new generation of scientists.

“This program originates from City of Hope’s longstanding expertise in conducting clinical trials and applying fundamental stem cell biology and gene therapy to the treatment of diseases. The program reflects City of Hope’s commitment to ensuring that future scientific leaders understand the varied needs of diverse patient populations, and the inequities that presently affect both biomedical research and the development of and access to innovative therapies.”

Students in the program will have access to world class research facilities and will also benefit from the fact that their classrooms and laboratories are within walking distance from where patients are treated. We believe the best scientists need to have experience in working both at the laboratory bench and at the bedside, not only developing new therapies, but being able to deliver those therapies in a caring, compassionate way.

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  

Breaking down barriers: Expanding patient access and accelerating research

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10 years ago I was presented with an incredibly unique opportunity- to become the fifth patient with spinal cord injuries to participate in the world’s first clinical trial testing a treatment made from human embryonic stem cells. It was not only a risky and potentially life-changing decision, but also one that I had to make in less than a week. 

To make matters more complicated, I was to be poked, prodded, and extensively scanned on a daily basis for several months as part of the follow-up process. I lived nearly two hours away from the hospital and I was newly paralyzed. How would this work? I wanted my decision-making process to be solely based on the amazing science and the potential that with my participation, the field might advance. Instead, I found myself spending countless hours contemplating the extra work I was asking my family to take on in addition to nursing me back to life. 

In this instance, I was “lucky”. I had access to family and friends who were able and willing to make any kind of sacrifice to ensure my happiness. I lived quite a distance away from the hospital, but everyone around me had a car. They had the means to skip work, keep the gas tank filled, and make the tedious journey. I also had an ally, which was perhaps my biggest advantage. The California Institute for Regenerative Medicine (CIRM) was the funding agency behind the groundbreaking clinical trial and I’ll never forget the kind strangers who sat on my bedside and delighted me with stories of hope and science. 

Accelerating the research

The field of regenerative medicine has gained so much momentum since my first introduction to stem cells in a small hospital room. Throughout the decade and especially in recent years there have been benchmark FDA approvals, increased funding and regulatory support. The passage of Proposition 14 in 2020 has positioned CIRM to continue to accelerate research from discovery to clinical and to drive innovative, real-world solutions resulting in transformative treatments for patients. 

Now, thanks to Prop 14 we have some new goals, including working to try and ensure that the treatments our funding helps develop are affordable and accessible to a diverse community of patients in an equitable manner, including those often overlooked or underrepresented in the past. Unsurprisingly, one of the big goals outlined in our new 5-year Strategic Plan is to deliver real world solutions through the expansion of the CIRM Alpha Stem Cell Clinics network and the creation of a network of Community Care Centers of Excellence.

The Alpha Stem Cell Clinics and Community Care Centers of Excellence will work in collaboration to achieve a wide set of goals. These goals include enabling innovative clinical research in regenerative medicine, increasing diverse patient access to transformative therapies, and improving patient navigation of clinical trials. 

Breaking down the barriers 

The dilemma surrounding the four-hour long round-trip journey for an MRI or a vial of blood isn’t just unique to me and my experience participating in a clinical trial. It is well recognized and documented that geographic disparities in clinical trial sites as well as limited focus on community outreach and education about clinical trials impede patient participation and contribute to the well-documented low participation of under-represented patients in clinical studies.

As outlined in our Strategic Plan, the Alpha Stem Cell Clinic Network and Community Care Centers will collaboratively extend geographic access to CIRM-supported clinical trials across the state. Community Care Centers will have direct access and knowledge about the needs of their patient populations including, culturally and linguistically effective community-based education and outreach. In parallel, Alpha Stem Cell Clinics will be designed to support the anticipated outreach and education efforts of future Community Care Centers.

To learn more about CIRM’s approach to deliver real world solutions for patients, check out our new 5-year Strategic Plan

Creating a diverse group of future scientists

Students in CIRM’s Bridges program showing posters of their work

If you have read the headlines lately, you’ll know that the COVID-19 pandemic is having a huge impact on the shipping industry. Container vessels are forced to sit out at anchor for a week or more because there just aren’t enough dock workers to unload the boats. It’s a simple rule of economics, you can have all the demand you want but if you don’t have the people to help deliver on the supply side, you are in trouble.

The same is true in regenerative medicine. The field is expanding rapidly and that’s creating a rising demand for skilled workers to help keep up. That doesn’t just mean scientists, but also technicians and other skilled individuals who can ensure that our ability to manufacture and deliver these new therapies is not slowed down.

That’s one of the reasons why CIRM has been a big supporter of training programs ever since we were created by the voters of California when they approved Proposition 71. And now we are kick-starting those programs again to ensure the field has all the talented workers it needs.

Last week the CIRM Board approved 18 programs, investing more than $86 million, as part of the Agency’s Research Training Grants program. The goal of the program is to create a diverse group of scientists with the knowledge and skill to lead effective stem cell research programs.

The awards provide up to $5 million per institution, for a maximum of 20 institutions, over five years, to support the training of predoctoral graduate students, postdoctoral trainees, and/or clinical trainees.

This is a revival of an earlier Research Training program that ran from 2006-2016 and trained 940 “CIRM Scholars” including:

• 321 PhD students
• 453 Postdocs
• 166 MDs

These grants went to academic institutions from UC Davis in Sacramento to UC San Diego down south and everywhere in-between. A 2013 survey of the students found that most went on to careers in the industry.

  • 56% continued to further training
  • 14% advanced to an academic research faculty position
  • 10.5% advanced to a biotech/industry position
  • 12% advanced to a non-research position such as teaching, medical practice, or foundation/government work

The Research Training Grants go to:

AWARDINSTITUTIONTITLEAMOUNT
EDUC4-12751Cedars-SinaiCIRM Training Program in Translational Regenerative Medicine    $4,999,333
EDUC4-12752UC RiversideTRANSCEND – Training Program to Advance Interdisciplinary Stem Cell Research, Education, and Workforce Diversity    $4,993,115
EDUC4-12753UC Los AngelesUCLA Training Program in Stem Cell Biology    $5 million
EDUC4-12756University of Southern CaliforniaTraining Program Bridging Stem Cell Research with Clinical Applications in Regenerative Medicine    $5 million
EDUC4-12759UC Santa CruzCIRM Training Program in Systems Biology of Stem Cells    $4,913,271
EDUC4-12766Gladstone Inst.CIRM Regenerative Medicine Research Training Program    $5 million
EDUC4-12772City of HopeResearch Training Program in Stem Cell Biology and Regenerative Medicine    $4,860,989
EDUC4-12782StanfordCIRM Scholar Training Program    $4,974,073
EDUC4-12790UC BerkeleyTraining the Next Generation of Biologists and Engineers for Regenerative Medicine    $4,954,238
EDUC4-12792UC DavisCIRM Cell and Gene Therapy Training Program 2.0    $4,966,300
EDUC4-12802Children’s Hospital of Los AngelesCIRM Training Program for Stem Cell and Regenerative Medicine Research    $4,999,500
EDUC4-12804UC San DiegoInterdisciplinary Stem Cell Training Grant at UCSD III    $4,992,446
EDUC4-12811ScrippsTraining Scholars in Regenerative Medicine and Stem Cell Research    $4,931,353
EDUC4-12812UC San FranciscoScholars Research Training Program in Regenerative Medicine, Gene Therapy, and Stem Cell Research    $5 million
EDUC4-12813Sanford BurnhamA Multidisciplinary Stem Cell Training Program at Sanford Burnham Prebys Institute, A Critical Component of the La Jolla Mesa Educational Network    $4,915,671  
EDUC4-12821UC Santa BarbaraCIRM Training Program in Stem Cell Biology and Engineering    $1,924,497
EDUC4-12822UC IrvineCIRM Scholars Comprehensive Research Training Program  $5 million
EDUC4-12837Lundquist Institute for Biomedical InnovationStem Cell Training Program at the Lundquist Institute    $4,999,999

These are not the only awards we make to support training the next generation of scientists. We also have our SPARK and Bridges to Stem Cell Research programs. The SPARK awards are for high school students, and the Bridges program for graduate or Master’s level students.

Mother and daughter team up to fight bias and discrimination in treatment for people with sickle cell disease

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Adrienne Shapiro and Marissa Cors are a remarkable pair by any definition. The mother and daughter duo share a common bond, and a common goal. And they are determined not to let anyone stop them achieving that goal.

Marissa was born with sickle cell disease (SCD) a life-threatening genetic condition where normally round, smooth red blood cells are instead shaped like sickles. These sickle cells are brittle and can clog up veins and arteries, blocking blood flow, damaging organs, and increasing the risk of strokes. It’s a condition that affects approximately 100,000 Americans, most of them Black.

Adrienne became a patient advocate, founding Axis Advocacy, after watching Marissa get poor treatment in hospital Emergency Rooms.  Marissa often talks about the way she is treated like a drug-seeker simply because she knows what medications she needs to help control excruciating pain on her Sickle Cell Experience Live events on Facebook.

Now the two are determined to ensure that no one else has to endure that kind of treatment. They are both fierce patient advocates, vocal both online and in public. And we recently got a chance to sit down with them for our podcast, Talking ‘Bout (re) Generation. These ladies don’t pull any punches.

Enjoy the podcast.

CIRM is funding four clinical trials aimed at finding new treatments and even a cure for sickle cell disease.

City of Hope researchers discover potential therapy to treat brain tumors

Glioblastoma (GBM) is a common type of aggressive brain tumor that is found in adults.  Survival of this type of brain cancer is poor with just 40% survival in the first-year post diagnosis and 17% in the second year, according to the American Association of Neurological Surgeons.  This disease has taken the life of former U.S. Senator John McCain and Beau Biden, the late son of U.S. President Joe Biden.

In a CIRM supported lab that conducted the study, Dr. Yanhong Shi and her team at City of Hope, a research and treatment center for cancer, have discovered a potential therapy that they have tested that has been shown to suppress GBM tumor growth and extend the lifespan of tumor-bearing mice. 

Dr. Shi and her team first started by looking at PUS7, a gene that is highly expressed in GBM tissue in comparison to normal brain tissue.  Dr. Qi Cui, a scientist in Dr. Shi’s team and the first author of the study, analyzed various databases and found that high levels of PUS7 have also been associated with worse survival in GBM patients.  The team then studied different glioblastoma stem cells (GSCs), which play a vital role in brain tumor growth, and found that shutting off the PUS7 gene prevented GSC growth and self-renewal. 

The City of Hope team then transplanted two kinds of GSCs, some with the PUS7 gene and some with the PUS7 gene turned off, into immunodeficient mice.  What they found was that the mice implanted with the PUS7-lacking GSCs had less tumor growth and survived longer compared to the mice with the control GSCs that had PUS7 gene.

The team then proceeded to look for an inhibitor of PUS7 from a database of thousands of different compounds and drugs approved by the Food and Drug Administration (FDA).  After identifying a promising compound, the researchers tested the potential therapy in mice implanted with GSCs with the PUS7 gene.  What they found was remarkable.  The therapy inhibited the growth of brain tumors in the mice and their survival was significantly prolonged.

“This is one of the most important studies in my lab in recent years and the first paper to show a causal link between PUS7-mediated modification and cancer in general and GBM in particular” says Dr. Shi.  “It will be a milestone study for RNA modification in cancer.”

The full study was published in Nature Cancer.

Dr. Shi has previously worked on several CIRM-funded research projects, such as looking at a potential link between COVID-19 and a gene for Alzheimer’s as well as the development of a therapy for Canavan disease.

Learning life lessons in the lab

Rohan Upadhyay, CIRM SPARK student 2021

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.

SPARKing the genius of the next generation of scientists

Dr. Kelly Shepard, SPARK program director

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.

City of Hope scientists use stem cells to develop ‘mini-brains’ to study Alzheimer’s and to test drugs in development

Alzheimer’s is a progressive disease that destroys memory and other important mental functions. According to the non-profit HFC, co-founded by CIRM Board member Lauren Miller Rogen and her husband Seth Rogen, more than 5 million Americans are living with Alzheimer’s. It is the 6th leading cause of death in the U.S and it is estimated that by 2050 as many as 16 million Americans will have the disease. Alzheimer’s is the only cause of death among the top 10 in the U.S. without a way to prevent, cure, or even slow its progression, which is it is crucial to better understand the disease and to develop and test potential treatments.

It is precisely for this reason that researchers led by Yanhong Shi, Ph.D. at City of Hope have developed a ‘mini-brain’ model using stem cells in order to study Alzheimer’s and to test drugs in development.

The team was able to model sporadic Alzheimer’s, the most common form of the disease, by using human induced pluripotent stem cells (iPSCs), a kind of stem cell that can be created from skin or blood cells of people through reprogramming and has the ability to turn into virtually any other kind of cell. The researchers used these iPSCs to create ‘mini-brains’, also known as brain organoids, which are 3D models that can be used to analyze certain features of the human brain. Although they are far from perfect replicas, they can be used to study physical structure and other characteristics. 

The scientists exposed the ‘mini-brains’ to serum that mimics age-associated blood-brain barrier (BBB) breakdown. The BBB is a protective barrier that surrounds the brain and its breakdown has been associated with Alzheimer’s and other age-related neurodegenerative diseases . After exposure, the team tested the ‘mini-brains’ for various Alzheimer’s biomarkers. These markers included elevated levels of proteins known as amyloid and tau that are associated with the disease and synaptic breaks linked to cognitive decline.

Research using brain organoids has shown that exposure to serum from blood could induce multiple Alzheimer’s symptoms. This suggests that combination therapies targeting multiple areas would be more effective than single-target therapies currently in development.

The team found that attempting a single therapy, such as inhibiting only amyloid or tau proteins, did not reduce the levels of tau or amyloid, respectively. These findings suggest that amyloid and tau likely cause disease progression independently. Furthermore, exposure to serum from blood, which mimics BBB breakdown, could cause breaks in synaptic connections that help brains remember things and function properly.

Image Description: Yanhong Shi, Ph.D.

In a press release from the Associated Press, Dr. Shi elaborated on the importance of their model for studying Alzheimer’s.

“Drug development for Alzheimer’s disease has run into challenges due to incomplete understanding of the disease’s pathological mechanisms. Preclinical research in this arena predominantly uses animal models, but there is a huge difference between humans and animals such as rodents, especially when it comes to brain architecture. We, at City of Hope, have created a miniature brain model that uses human stem cell technology to study Alzheimer’s disease and, hopefully, to help find treatments for this devastating illness.”

The full results of this study were published in Advance Science.

Dr. Shi has previously worked on several CIRM-funded research projects, such as looking at a potential link between COVID-19 and a gene for Alzheimer’s as well as the development of a therapy for Canavan disease.

An Open Letter to CIRM for World Sickle Cell Day

Nancy M. Rene

Dear CIRM,

World Sickle Cell Day is this Saturday June 19th. The goal of this day is to increase knowledge of the disease and understanding of the challenges faced.

It is a day that I greet with very mixed feelings.  I’m of course extremely grateful to CIRM for the time and money spent looking for a cure.  The work of doctors, of researchers, the courage of families in the sickle cell community who are taking part in studies, and of course those of you who worked so hard for the original funding for CIRM, I applaud all of you, yet it’s hard to wait for a cure.

While I wait I worry. I worry about my friends who are not getting good care.  They are the ones who can’t find a doctor to treat them, not able to take advantage of the medications that are already approved.  They are the ones who walk into the Emergency Room hoping for knowledgeable treatment while understanding that they may be accused of being a drug seeker,  turned away in excruciating pain. They are the ones who succumb after years of poor care.

With sickle cell disease there is the same level of understanding about medical malpractice that we had of police brutality before George Floyd. We hardly remember Rodney King or Eric Garner. As a country we were aware that something was wrong but we tended to retreat in denial after each terrible headline.

That’s where we are with sickle cell disease.  We may see a heart-wrenching story and watch televised reports with interest, but after all, it’s easier to live in disbelief, to think that medical care is not that bad, rather than understand that people are being dismissed and denied treatment. We call it structural racism without understanding what that term really means.

While I wait I must acknowledge that change is coming.  We have a Sickle Cell Data Collection Project in California that helps us track healthcare for sickle cell disease. This is data that we can use to point to structural weakness and address health disparities.  NASEM, the National Academies of Science Engineering and Medicine, has published a huge report with significant suggestions for improving sickle cell care. Many scientists, researchers and advocates took part in this landmark study, detailing what has gone wrong in health care and how to improve the work. And of course we have CIRM. I am very thankful for the leadership and pioneering work of doctors Donald Kohn, Matthew Porteus, Mark Walters, and Joseph Rosenthal who are using their knowledge and experience in this fight.

When we have successful research on stem cell transplants for sickle cell disease, many of us with sickle cell family members will want to relax, but we can’t forget those who may not be able to get a curative transplant. I hope Dr Niihara at Emmaus, and Dr. Love of Global Blood Therapeutics will continue their important work finding effective treatments. We must continue this fight on all fronts.

World Sickle Cell Day will come again next year.  Let’s see what it brings.

A sickle cell grandmother,

Nancy M. René