Cedars-Sinai

CIRM-funded stem cell-gene therapy shows promise in ALS safety trial

/ Esteban Cortez / 1 Comment
Senior author of the study Clive Svendsen, PhD (center)

With funding support from the California Institute for Regenerative Medicine (CIRM), Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This combined stem cell and gene therapy can potentially protect diseased motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis, a fatal neurological disorder known as ALS or Lou Gehrig’s disease. 

In the first trial of its kind, the Cedars-Sinai team showed that delivery of this combined treatment is safe in humans. The findings were reported in the peer-reviewed journal Nature Medicine. 

What causes ALS? 

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. About 6,000 people are diagnosed with ALS each year in the U.S., and the average survival time is two to five years.  

The disease results when the cells in the brain or spinal cord that instruct muscles to move—called motor neurons—die off. People with the disease lose the ability to move their muscles and, over time, the muscles atrophy and people become paralyzed and eventually die. There is no effective therapy for the disease. 

Using Stem Cells to Treat ALS 

In a news release, senior author Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, says using stem cells shows lots of promise in treating patients with ALS.  

“We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect motor neurons that die in ALS,” Svendsen says.  

Aimed at preserving leg function in patients with ALS, the engineered cells could pave the way to a therapeutic option for this disease that causes progressive muscle paralysis, robbing people of their ability to move, speak and breathe.   

The study used stem cells originally designed in Svendsen’s laboratory to produce a protein called glial cell line-derived neurotrophic factor (GDNF). This protein can promote the survival of motor neurons, which are the cells that pass signals from the brain or spinal cord to a muscle to enable movement.  

In patients with ALS, diseased glial cells can become less supportive of motor neurons, and these motor neurons progressively degenerate, causing paralysis.   

By transplanting the engineered protein-producing stem cells in the central nervous system, where the compromised motor neurons are located, these stem cells can turn into new supportive glial cells and release the protective protein GDNF, which together helps the motor neurons stay alive.   

Ensuring Safety in the Trial 

The primary goal of the trial was to ensure that delivering the cells releasing GDNF to the spinal cord did not have any safety issues or negative effects on leg function.   

In this trial, none of the 18 patients treated with the therapy—developed by Cedars-Sinai scientists and funded by CIRM—had serious side effects after the transplantation, according to the data. 

Because patients with ALS usually lose strength in both legs at a similar rate, investigators transplanted the stem cell-gene product into only one side of the spinal cord so that the therapeutic effect on the treated leg could be directly compared to the untreated leg.  

After the transplantation, patients were followed for a year so the team could measure the strength in the treated and untreated legs. The goal of the trial was to test for safety, which was confirmed, as there was no negative effect of the cell transplant on muscle strength in the treated leg compared to the untreated leg.    

What’s Next? 

Investigators expect to start a new study with more patients soon. They will be targeting lower in the spinal cord and enrolling patients at an earlier stage of the disease to increase the chances of seeing effects of the cells on the progression of ALS. 

“We are very grateful to all the participants in the study,” said Svendsen. “ALS is a very tough disease to treat, and this research gives us hope that we are getting closer to finding ways to slow down this disease.”   

The Cedars-Sinai team is also using the GDNF-secreting stem cells in another CIRM-funded clinical trial for ALS, transplanting the cells into a specific brain region, called the motor cortex that controls the initiation of movement in the hand. The clinical trial is also funded by CIRM. 

The California Institute for Regenerative Medicine (CIRM) remains committed to funding research and clinical trials to treat ALS. To date, CIRM has provided $93 million in funding for research to treat ALS.  

Read the original source release of the study here.  

Using reengineered human skin cells to treat COVID-19

/ Esteban Cortez / 1 Comment

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Investigators at Cedars-Sinai have identified a potential new therapy for COVID-19: a biologic substance created by reengineered human skin cells.   

In the study—co-funded by the California Institute for Regenerative Medicine (CIRM)—scientists found the substance stopped SARS-CoV-2, the virus that causes COVID-19, from reproducing itself. The substance also protected infected cells when tested in human lung cells.  

Although still in the early stages, the findings open the possibility of having a new therapy for COVID-19 patients, of which there are few. Current COVID-19 treatments primarily focus on preventing the virus from replicating. This new potential treatment inhibits replication but also protects or repairs tissue, which is important because COVID-19 can cause symptoms that affect patients long after the viral infection has been cleared. 

The potential therapy investigated in this study was created by scientists using skin cells called dermal fibroblasts. The investigators engineered the cells to produce therapeutic extracellular vesicles (EVs), which are nanoparticles that serve as a communication system between cells and tissue. Engineering these fibroblasts allowed them to secrete EVs—which the investigators dubbed “ASTEX”—with the ability to repair tissue. 

The study tested ASTEX by applying it to human lung epithelial cells, cells that line the pulmonary tract and are the targets of SARS-CoV-2 infection. They discovered that ASTEX prevented cells from launching an inflammatory process that could lead to cell death. Cells treated with ASTEX also made fewer of a type of protein called ACE that SARS-CoV-2 may use to infect cells. 

The team compared the new potential treatment with remdesivir, a drug currently used to treat COVID-19, and found that remdesivir did not inhibit production of ACE. Instead, remdesivir stops the virus from latching on to a protein called ACE2. ASTEX, therefore, may present another way to prevent the virus from entering cells. 

“We were surprised to find this potential therapy shuts down a novel pathway for viral replication and also protects infected cells,” said Ahmed G. Ibrahim, PhD, MPH, assistant professor in the Smidt Heart Institute at Cedars-Sinai and first author of the study. 

Investigators at Cedars-Sinai are planning future studies.  

The details of the potential therapy are published in the journal Biomaterials and Biosystems. Read the source article here. 

Stem cell discovery could help shorten cancer treatment recovery 

/ Esteban Cortez / 1 Comment

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

A researcher prepares to study blood cells under a microscope. Photo by Getty.

A recent discovery by stem cell scientists at Cedars-Sinai may help make cancer treatment more efficient and shorten the time it takes for people to recover from radiation and chemotherapy.  

Published in the journal Nature Communications, the study by Dr. John Chute and his team (and co-funded by CIRM) revealed a mechanism through which the blood vessels in the bone marrow respond to injury, such as from chemotherapy or radiation. 

Each year, about 650,000 cancer patients receive chemotherapy in an outpatient oncology clinic in the United States.  

When people receive radiation or chemotherapy as part of their cancer treatment, their blood counts plummet. It typically takes several weeks for these counts to return to normal levels. During this period patients are at risk for developing infections that may lead to hospitalization, disruptions in chemotherapy schedules, and even death. 

Chute and his colleagues found that when mice receive radiation treatment, the cells that line the inner walls of the blood vessels in the bone marrow produce a protein called semaphorin 3A. This protein tells another protein, called neuropilin 1, to kill damaged blood vessels in the bone marrow. 

When the investigators blocked the ability of these blood vessel cells to produce neuropilin 1 or semaphorin 3A, or injected an antibody that blocks semaphorin 3A communication with neuropilin 1, the veins and arteries in the bone marrow regenerated faster following irradiation. In addition, blood counts increased dramatically after one week. 

“We’ve discovered a mechanism that appears to control how blood vessels regenerate following injury,” said Chute, senior author of the paper. “Inhibiting this mechanism causes rapid recovery of the blood vessels and blood cells in bone marrow following chemotherapy or irradiation.”  

In principle, Chute said, targeting this mechanism could allow patients to recover following chemotherapy in one to two weeks, instead of three or four weeks as currently experienced. 

Christina M. Termini, a post-doctoral scientist at the David Geffen School of Medicine at UCLA, was the first author of this study. Read the source press release here.  

Creating a diverse group of future scientists

/ Kevin McCormack / Leave a comment
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.

SPARKing the genius of the next generation of scientists

/ Kevin McCormack / 4 Comments
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.

You can’t take it if you don’t make it

/ Kevin McCormack / Leave a comment
Biomedical specialist Mamadou Dialio at work in the Cedars-Sinai Biomanufacturing Center. Photo by Cedars-Sinai.

Following the race to develop a vaccine for COVID-19 has been a crash course in learning how complicated creating a new therapy is. It’s not just the science involved, but the logistics. Coming up with a vaccine that is both safe and effective is difficult enough, but then how do you make enough doses of it to treat hundreds of millions of people around the world?

That’s a familiar problem for stem cell researchers. As they develop their products they are often able to make enough cells in their own labs. But as they move into clinical trials where they are testing those cells in more and more people, they need to find a new way to make more cells. And, of course, they need to plan ahead, hoping the therapy is approved by the Food and Drug Administration, so they will need to be able to manufacture enough doses to meet the increased demand.

We saw proof of that planning ahead this week with the news that Cedars-Sinai Medical Center in Los Angeles has opened up a new Biomanufacturing Center.

Dr. Clive Svendsen, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in a news release, the Center will manufacture the next generation of drugs and regenerative medicine therapies.

“The Cedars-Sinai Biomanufacturing Center leverages our world-class stem-cell expertise, which already serves scores of clients, to provide a much-needed biomanufacturing facility in Southern California. It is revolutionary by virtue of elevating regenerative medicine and its therapeutic possibilities to an entirely new level-repairing the human body.”

This is no ordinary manufacturing plant. The Center features nine “clean rooms” that are kept free from dust and other contaminants. Everyone working there has to wear protective suits and masks to ensure they don’t bring anything into the clean rooms.

The Center will specialize in manufacturing induced pluripotent stem cells, or iPSCs. Dhruv Sareen, PhD, executive director of the Biolmanufacturing Center, says iPSCs are cells that can be turned into any other kind of cell in the body.

“IPSCs are powerful tools for understanding human disease and developing therapies. These cells enable us to truly practice precision medicine by developing drug treatments tailored to the individual patient or groups of patients with similar genetic profiles.”

The Biomanufacturing Center is designed to address a critical bottleneck in bringing cell- and gene-based therapies to the clinic. After all, developing a therapy is great, but it’s only half the job. Making enough of it to help the people who need it is the other half.

CIRM is funding Dr. Svendsen’s work in developing therapies for ALS and other diseases and disorders.  

Mind altering, life changing experience in stem cell lab

/ Kevin McCormack / Leave a comment

This week we are featuring the best blogs from our SPARK (Summer Program to Accelerate Regenerative medicine Knowledge) students. SPARK gives high school students a chance to spend their summer working in a world class stem cell research facility here in California. In return they write about their experiences and what they learned.

The blog that won second place comes from Emily Bunnapradist who spent her summer at Cedars-Sinai Medical Center in Los Angeles.

Emily Bunnapradist by the poster presentation of her work

When I was in the third grade, my mom took me to the allergy wing in the UCLA Medical Center, hoping to find answers to a number of issues that accompanied my seemingly never-ending list of food allergies: dairy, eggs, nuts, legumes, and so on. Unexpectedly, without even an appointment, clinician Dr. Braskett spent an hour out of her already busy schedule just talking us through our worries in the lobby, checking out skin problems that arose as a result of my allergies and promising to see us again as soon as she could. Because of her overwhelming kindness and generosity, my mom and I went home with relieved smiles and assurance that my health concerns were manageable.

That was the day that I decided that I wanted to pursue medicine, to make an impact on people the way that she had on my family and me. However, my conception of the field of healthcare was quite limited. For the majority of my life, I was convinced that the only way to make a true connection in a patient’s well-being was as a clinician.

This unfounded claim quickly changed when I was accepted into the CIRM SPARK program at Cedars-Sinai. In the most action-packed summer I have ever had the opportunity to experience, I was exposed to the diverse field of healthcare. Transitioning between the clinical and research aspects of science, I saw firsthand the direct effect that researchers had on patients in fields I had not even considered.

While touring the blood transfusion facility at Cedars-Sinai, a technician proudly boasted about her connection to patient care in labeling and testing blood donations to ensure they were suitable for those in need. Upon viewing the imaging core, the manager of the center informed us about the revolutionary advances his team was making in developing software to identify cancerous indicators in patients. In visiting the microbiology lab, multiple lab scientists informed us about the hundreds of tests they perform on a daily basis to detect diseases such as influenza and adenovirus, without which clinicians wouldn’t be able to perform their job to the fullest degree.

In these past weeks, I have spent hundreds of hours in the lab. From drawing on sections with hydrophobic markers to loading gels with protein samples, I have gained tremendous experience in navigating a research environment. However, although I now know the mechanics of Western blots and immunostaining like the back of my hand, the most essential takeaways for me are not learning the procedures but understanding their applications. While I am now able to pipette fluids with a steady hand and make buffer solutions without second-guessing my calculations, I am also able to appreciate the science behind each protein band and cell plate. Being able to contribute to my project and hear about my peers’ experiments has shown me the scope of influence research can have on extending knowledge and generating cures to diseases.

While I had initially considered research to be cold and isolating, I have found more warmth and connection here than I believed possible. The passion that my mentors possess for their line of work, as well as their endless knowledge on essentially any topic imaginable, has shown me the importance and integrity of what they do.

The CIRM SPARK students at Cedars-Sinai (Emily is front right): Photo courtesy Cedars-Sinai

I could not be more grateful to have the guidance of Dr. Mehrnoosh Ghiam and Dr. Adam Poe, who I have formed strong relationships with and have helped me accomplish what I have this summer. Their mentorship, along with the resources of Cedars-Sinai, have granted me the most productive and exciting summer I’ve had yet!

Next generation of stem cell scientists leave their mark

/ Kevin McCormack / Leave a comment

One of the favorite events of the year for the team here at CIRM is our annual SPARK (Summer Program to Accelerate Regenerative Medicine Knowledge) conference. This is where high school students, who spent the summer interning at world class stem cell research facilities around California, get to show what they learned. It’s always an engaging, enlightening, and even rather humbling experience.

The students, many of whom are first generation Californians, start out knowing next to nothing about stem cells and end up talking as if they were getting ready for a PhD. Most say they went to their labs nervous about what lay ahead and half expecting to do menial tasks such as rinsing out beakers. Instead they were given a lab coat, safety glasses, stem cells and a specific project to work on. They learned how to handle complicated machinery and do complex scientific experiments.

But most importantly they learned that science is fun, fascinating, frustrating sometimes, but also fulfilling. And they learned that this could be a future career for them.

We asked all the students to blog about their experiences and the results were extraordinary. All talked about their experiences in the lab, but some went beyond and tied their internship to their own lives, their past and their hopes for the future.

Judging the blogs was a tough assignment, deciding who is the best of a great bunch wasn’t easy. But in the end, we picked three students who we thought captured the essence of the SPARK program. This week we’ll run all those blogs.

We begin with our third place blog by Dayita Biswas from UC Davis.

Personal Renaissance: A Journey from Scientific Curiosity to Confirmed Passions

By Dayita Biswas

As I poured over the pages of my battered Campbell textbook, the veritable bible for any biology student, I saw unbelievable numbers like how the human body is comprised of over 30 trillion cells! Or how we have over 220 different types of cells— contrary to my mental picture of a cell as a circle. Science, and biology in particular, has no shortage of these seemingly impossible Fermi-esque statistics that make one do a double-take. 

My experience in science had always been studying from numerous textbooks in preparation for a test or competitions, but textbooks only teach so much. The countless hours I spent reading actually demotivated me and I constantly asked myself what was the point of learning about this cycle or that process — the overwhelming “so what?” question. Those intriguing numbers that piqued my interest were quickly buried under a load of other information that made science a static stream of words across a page. 

That all changed this summer when I had the incredible opportunity to work in the Nolta lab under my mentor, Whitney Cary. This internship made science so much more tangible and fun to be a part of.  It was such an amazing environment, being in the same space with people who all have the same goals and passion for science that many high school students are not able to truly experience. Everyone was so willing to explain what they were doing, and even went out of their way to help if I needed papers or had dumb questions.

This summer, my project was to create embryoid bodies and characterize induced pluripotent stem cells (iPSCs) from children who had Jordan’s Syndrome, an extremely rare neurodevelopmental disease whose research has applications in Alzheimer’s and autism.

 I had many highs and lows during this research experience. My highs were seeing that my iPSCs were happy and healthy. I enjoyed learning lab techniques like micro-pipetting, working in a biological safety hood, feeding, freezing, and passaging cells. My lows were having to bleach my beloved iPSCs days after they failed to survive, and having unsuccessful protocols. However, while my project consistently failed, these failures taught me more than my successes.

I learned that there is a large gap between being able to read about techniques and being “book smart” and actually being able to think critically about science and perform research. Science, true science, is more than words on a page or fun facts to spout at a party. Science is never a straight or easy answer, but the mystery and difficulty is part of the reason it is so interesting. Long story short: research is hard and it takes time and patience, it involves coming in on weekends to feed cells, and staying up late at night reading papers.         

The most lasting impact that this summer research experience had was that everything we learn in school and the lab are all moving us towards the goal of helping real people. This internship renewed my passion for biology and cemented my dream of working in this field. It showed me that I don’t have to wait to be a part of dynamic science and that I can be a small part of something that will change, benefit, and save lives.

This internship meant being a part of something bigger than myself, something meaningful. We must always think critically about what consequences our actions will have because what we do as scientists and researchers— and human beings will affect the lives of real people. And that is the most important lesson anyone can hope to learn.

                                                                                                   

And here’s a bonus, a video put together by the SPARK students at Cedars-Sinai Medical Center.

Blood-brain barrier chip created with stem cells expands potential for personalized medicine

/ Yimy Villa / 1 Comment
An Organ-Chip used in the study to create a blood-brain barrier (BBB).

The brain is a complex part of the human body that allows for the formation of thoughts and consciousness. In many ways it is the essence of who we are as individuals. Because of its importance, our bodies have developed various layers of protection around this vital organ, one of which is called the blood-brain barrier (BBB).

The BBB is a thin border of various cell types around the brain that regulate what can enter the brain tissue through the bloodstream. Its primary purpose is to prevent toxins and other unwanted substances from entering the brain and damaging it. Unfortunately this barrier can also prevent helpful medications, designed to fix problems, from reaching the brain.

Several brain disorders, such as Amyotrophic Lateral Sclerosis (ALS – also known as Lou Gehrig’s disease), Parkinson’s Disease (PD), and Huntington’s Disease (HD) have been linked to defective BBBs that keep out critical biomolecules needed for healthy brain activity.

In a CIRM-funded study, a team at Cedars-Sinai Medical Center created a BBB through the use of stem cells and an Organ-Chip made from induced pluripotent stem cells (iPSCs). These are a specific type of stem cells that can turn into any type of cell in the body and can be generated from a person’s own cells. In this study, iPSCs were created from adult blood samples and used to make the neurons and other supporting cells that make up the BBB. These cells were then placed inside an Organ-Chip which recreates the environment that cells normally experience within the human body.

Inside the 3-D Organ-Chip, the cells were able to form a BBB that functions as it does in the body, with the ability to block entry of certain drugs. Most notably, when the BBB was generated from cell samples of patients with HD, the BBB malfunctioned in the same way that it does in patients with the disease.

These findings expand the potential for personalized medicine for various brain disorders linked to problems in the BBB. In a press release, Dr. Clive Svendsen, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and senior author of the study, was quoted as saying,

“The study’s findings open a promising pathway for precision medicine. The possibility of using a patient-specific, multicellular model of a blood barrier on a chip represents a new standard for developing predictive, personalized medicine.”

The full results of the study were published in the scientific journal Cell Stem Cell.

Advancing stem cell research in many ways

/ Kevin McCormack / 2 Comments
Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.