The long road to developing a therapy for epilepsy

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Good science takes time. That’s an important guiding phrase for researchers looking to develop new therapies. But it’s also a frustrating reality for patients who are waiting for something to help them now.

That point was driven home last week when the governing board of the California Institute for Regenerative Medicine (CIRM) voted to invest almost $8 million to test a new approach to treating a drug-resistant form of epilepsy. This approach holds a lot of promise but getting to this point has not been easy or quick.

Epilepsy is one of the most common neurological disorders in the US, affecting more than three million people. More than one third of those people have a form of epilepsy that doesn’t respond to current medications, so the only options are surgery or using lasers (LITT) to remove the affected part of the brain. Not surprisingly this can cause serious, irreversible damage, such as effects on memory, mood and vision. Equally unsurprising, because of those impacts many people are reluctant to go that route.

Now a company called Neurona Therapeutics has developed a new approach called NRTX-1001. This consists of a specialized type of neuronal or brain cell that is derived from embryonic stem cells (hESCs).  These neuronal cells are injected into the brain in the area affected by the seizures where they release a neurotransmitter or chemical messenger that will block the signals in the brain causing the epileptic seizures. Pre-clinical testing suggests a single dose of NRTX-1001 may have a long-lasting ability to suppress seizures.

Cory Nicholas, PhD, the Co-Founder and CEO of Neurona says this approach will be tested on people with drug-resistant temporal lobe epilepsy, the most common form of epilepsy.

“To our knowledge, NRTX-1001 is the first human cell therapy to enter clinical trials for epilepsy. This cell therapy has the potential to provide a less invasive, non-tissue destructive, regenerative alternative for people with chronic focal seizures.” 

“Epilepsy patient advocates and clinicians have said that such a regenerative cell therapy could represent a first option that, if successful, could obviate the need for lobectomy/LITT. And for those not eligible for lobectomy/LITT, cell therapy could provide the only option to potentially achieve seizure-freedom.”

Nicholas says this work didn’t happen overnight. “This effort to develop regenerative cell therapy for epilepsy officially began in the early 2000’s from the laboratories of John Rubenstein, MD, PhD, Arturo Alvarez-Buylla, PhD, and Arnold Kriegstein, MD, PhD, at UC San Francisco. They were among the first to understand how specialized inhibitory nerve cells, called interneurons, develop from neural stem cells in our forebrain before birth. Subsequently, they pioneered the extraction and use of these cells as a cell therapy in preclinical models.”

Over the years the group working on this approach expanded, later becoming Neurona Therapeutics, and CIRM supported that work with several awards.

“CIRM provided the necessary funds and expertise to help translate our discoveries toward the clinic using human embryonic stem cell (hESC) technology to generate a sustainable supply of interneuron cells for further evaluation. Truly, CIRM has been the essential catalyst in accelerating this important research from bench to bedside.”

Nicholas says its immensely gratifying to be part of this work, and to know that if it succeeds it will be life-altering, even life-saving, for so many people.

“It is difficult to reflect back with all the work that is happening at present on the first-in-human trial, but it is always emotional for me to think about our amazing team: Neurona employees, CIRM staff, clinicians, professors, trainees, collaborators, and investors; who have worked tirelessly in contributing to the advancement of this therapeutic mission. I am deeply humbled by the opportunity to be part of this innovative, rigorous, and compassionate effort, and by the responsibility to the brave patients participating in the study. We remain steadfast in our commitment to patient safety and cautiously optimistic that NRTX-1001 cell therapy will improve quality of life for people living with chronic focal epilepsy. Moreover, we are sincerely thankful to Californians for their commitment to CIRM’s vision, and we are proud to be a part of this groundbreaking initiative that has put our state at the forefront, dedicated to fulfilling the promise of regenerative medicine.”

CIRM-Funded Study Helping Babies Battle a Deadly Immune Disorder Gets Boost from FDA

Hataalii Begay, age 4, first child treated with UCSF gene therapy for Artemis-SCID

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When Hataalii Begay was born in a remote part of the Navajo nation he was diagnosed with a rare, usually fatal condition. Today, thanks to a therapy developed at UCSF and funded by CIRM, he’s a normal healthy four year old boy running around in cowboy boots.

That stem cell therapy could now help save the lives of other children born with this deadly immune disorder because it has been granted fast-track review status by the US Food and Drug Administration (FDA).

The California Institute for Regenerative Medicine (CIRM) has invested $12 million to test this therapy in a clinical trial at UC San Francisco.

The disorder is Artemis-SCID, a form of severe combined immunodeficiency disease. Children born with this condition have no functioning immune system so even a simple infection can prove life-threatening or fatal.

Currently, the only approved treatment for Artemis-SCID is a bone-marrow transplant, but many children are unable to find a healthy matched donor for that procedure. Even when they do find a donor they often need regular injections of immunoglobulin to boost their immune system.

In this clinical trial, UCSF Doctors Mort Cowan and Jennifer Puck are using the patient’s own blood stem cells, taken from their bone marrow. In the lab, the cells are modified to correct the genetic mutation that causes Artemis-SCID and then re-infused back into the patients. The goal is that over the course of several months these cells will create a new blood supply, one that is free of Artemis-SCID, and that will in turn help repair the child’s immune system.

So far the team has treated ten newly-diagnosed infants and three older children who failed transplants. Dr. Cowan says early data from the trial is encouraging. “With gene therapy, we are seeing these babies getting older. They have normal T-cell immunity and are getting immunized and vaccinated. You wouldn’t know they had any sort of condition if you met them; it’s very heartening.”

Because of that encouraging data, the FDA is granting this approach Regenerative Medicine Advanced Therapy (RMAT) designation. RMAT is a fast-track designation that can help speed up the development, review and potential approval of treatments for serious or life-threatening diseases.

“This is great news for the team at UCSF and in particular for the children and families affected by Artemis-SCID,” says Dr. Maria T. Millan, the President and CEO of CIRM. “The RMAT designation means that innovative forms of cell and gene therapies like this one may be able to accelerate their route to full approval by the FDA and be available to all the patients who need it.”

CIRM Board gives thumbs up to training and treatment programs

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CIRM Bridges student discusses her poster presentation

At CIRM, the bread and butter of what we do is funding research and hopefully advancing therapies to patients. But the jam, that’s our education programs. Helping train the next generation of stem cell and gene therapy scientists is really inspiring. Watching these young students – and some are just high school juniors – come in and grasp the science and quickly become fluent in talking about it and creating their own experiments shows the future is in good hands.

Right now we fund several programs, such as our SPARK and Bridges internships, but they can’t cover everything, so last week the CIRM Board approved a new training program called COMPASS (Creating Opportunities through Mentorship and Partnership Across Stem Cell Science). The program will fill a critical need for skilled research practitioners who understand and contribute at all levels in the translation of science to medicine, from bench to bedside.

The objective of the COMPASS Training Program is to prepare a diverse group of undergraduate students for careers in regenerative medicine through the creation of novel recruitment and support mechanisms that identify and foster untapped talent within populations that are historically under-represented in the biomedical sciences. It will combine hands-on research with mentorship experiences to enhance transition of students to successful careers. A parallel objective is to foster greater awareness and appreciation of diversity, equity and inclusion in trainees, mentors, and other program participants

The CIRM Board approved investing $58.22 million for up to 20 applications for a five-year duration.

“This new program highlights our growing commitment to creating a diverse workforce, one that taps into communities that have been historically under-represented in the biomedical sciences,” says Dr. Maria T. Millan, President and CEO of CIRM. “The COVID19 pandemic made it clear that the benefits of scientific discovery are not always accessible to communities that most need them. CIRM is committed to tackling these challenges by creating a diverse and dedicated workforce that can meet the technical demands of taking novel treatment ideas and making them a reality.”

The Board also approved a new $80 million concept plan to expand the CIRM Alpha Stem Cell Clinic Network. The Network clinics are all in top California medical centers that have the experience and the expertise to deliver high-quality FDA-authorized stem cell clinical trials to patients.

There are currently five Alpha Clinics – UC San Diego; UCLA/UC Irvine; City of Hope; UCSF; UC Davis – and since 2015 they have hosted more than 105 clinical trials, enrolled more than 750 patients in these trials, and generated more than $95 million in industry contracts. 

Each award will provide up to $8 million in funding over a five-year period. The clinics will have to include:

  • A demonstrated ability to offer stem cell and gene therapies to patients as part of a clinical trial.
  • Programs to help support the career development of doctors, nurses, researchers or other medical professionals essential for regenerative medicine clinical trials.
  • A commitment to data sharing and meeting CIRM’s requirements addressing issues of diversity, equity and inclusion and meeting the needs of California’s diverse patient population.

National Academy of Medicine honors CIRM Grantees

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As someone who is not always as diligent as he would like to be about sending birthday cards on time, I’m used to sending belated greetings to people. So, I have no shame in sending belated greetings to four CIRM grantees who were inducted into the National Academy of Medicine in 2020.

I say four, but it’s really three and a half. I’ll explain that later.

Being elected to the National Academy of Medicine is, in the NAM’s own modest opinion, “considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.”

To be fair, NAM is right. The people elected are among the best and brightest in their field and membership is by election from the other members of NAM, so they are not going to allow any old schmuck into the Academy (which could explain why I am still waiting for my membership).

The CIRM grantees elected last year are:

Dr. Antoni Ribas: Photo courtesy UCLA

Antoni Ribas, MD, PhD, professor of medicine, surgery, and molecular and medical pharmacology, U. C. Los Angeles.

Dr. Ribas is a pioneer in cancer immunology and has devoted his career to developing new treatments for malignant melanoma. When Dr. Ribas first started malignant melanoma was an almost always fatal skin cancer. Today it is one that can be cured.

In a news release Dr. Ribas said it was a privilege to be honored by the Academy: “It speaks to the impact immunotherapy has played in cancer research. When I started treating cases of melanoma that had metastasized to other organs, maybe 1 in 20 responded to treatment. Nobody in their right mind wanted to be a specialist in this field. It was the worst of the worst cancers.”

Looks like he chose his career path wisely.

Dr. Jeffrey Goldberg: Photo courtesy Stanford

Jeffrey Louis Goldberg, MD, PhD, professor and chair of ophthalmology, Stanford University, Palo Alto, Calif.

Dr. Goldberg was honored for his contribution to the understanding of vision loss and ways to reverse it. His lab has developed artificial retinas that transmit images down the optic nerve to the brain through tiny silicon chips implanted in the eye. He has also helped use imaging technology to better improve our ability to detect damage in photoreceptor cells (these are cells in the retina that are responsible for converting light into signals that are sent to the brain and that give us our color vision and night vision)

In a news release he expressed his gratitude saying: “I look forward to serving the goals of the National Academies, and to continuing my collaborative research efforts with my colleagues at the Byers Eye Institute at Stanford and around the world as we further our efforts to combat needless blindness.”

Dr. Mark Anderson; photo courtesy UCSF

Mark S. Anderson, MD, PhD, professor in Diabetes Research, Diabetes Center, U. C. San Francisco.

Dr. Anderson was honored for being a leader in the study of autoimmune diseases such as type 1 diabetes. This focus extends into the lab, where his research examines the genetic control of autoimmune diseases to better understand the mechanisms by which immune tolerance is broken.

Understanding what is happening with the immune system, figuring out why it essentially turns on the body, could one day lead to treatments that can stop that, or even reverse it by boosting immune activity.

Dr. John Dick: Photo courtesy University Health Network, Toronto

Remember at the beginning I said that three and a half CIRM grantees were elected to the Academy, well, Canadian researcher, Dr. John Dick is the half. Why? Well, because the award we funded actually went to UC San Diego’s Dennis Carson but it was part of a Collaborative Funding Partnership Program with Dr. Dick at the University of Toronto. So, we are going to claim him as one of our own.

And he’s a pretty impressive individual to partner with. Dr. Dick is best known for developing a test that led to the discovery of leukemia stem cells. These are cells that can evade surgery, chemotherapy and radiation and which can lead to patients relapsing after treatment. His work helped shape our understanding of cancer and revealed a new strategy for curing it.

Creating a better way to treat type 1 diabetes

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The cell encapsulation device (right) that is being developed by Encellin, a San Francisco–based biotechnology company. Photo courtesy of Encellin

Type 1 diabetes (t1d) affects every aspect of a person’s life, from what they eat and when they eat, to when they exercise and how they feel physically and emotionally. Because the peak age for being diagnosed with t1d is around 13 or 14 years of age it often hits at a time when a child is already trying to cope with big physical and emotional changes. Add in t1d and you have a difficult time made a lot more challenging.

There are ways to control the disease. Regular blood sugar monitoring and insulin injections can help people manage their condition but those come with their own challenges. Now researchers are taking a variety of different approaches to developing new, innovative ways of helping people with t1d.

One of those companies is Encellin. They are developing a pouch-like device that can be loaded with stem cells and then implanted in the body. The pouch acts like a mini factory, releasing therapies when they are needed.

This work began at UC San Francisco in the lab of Dr. Tejal Desai – with help from CIRM funding – that led to the creation of Encellin. We recently sat down – virtually of course – with Dr. Grace Wei, the co-founder of the company to chat about their work, and their hopes for the future.

Dr. Grace Wei

She said the decision to target t1d was an easy one:

Type 1 diabetes is an area of great need. It’s very difficult to manage at any age but particularly in children. It affects what they can eat, what they can do, it’s a big burden on the family and can become challenging to manage when people get older.

“It’s an autoimmune disease so everyone’s disease progression is a bit different. People think it’s just a matter of you having too much blood sugar and not enough insulin, but the problem with medicines like insulin is that they are not dynamic, they don’t respond to the needs of your body as they occur. That means people can over-regulate and give themselves too much insulin for what their body needs and if it happens at night, it can be deadly.

Dr. Wei says stem cell research opens up the possibility of developing dynamic therapies, living medicines that are delivered to you by cells that respond to your dynamic needs. That’s where their pouch, called a cell encapsulation device (CED) comes in.

The pouch is tiny, only about the size of a quarter, and it can be placed just under the skin. Encellin is filling the pouch with glucose-sensitive, insulin producing islet cells, the kind of cells destroyed by t1d. The idea is that the cells can monitor blood flow and, when blood sugar is low, secrete insulin to restore it to a healthy level. 

Another advantage of the pouch is that it may eliminate the need for the patient to take immunosuppressive medications.

“The pouch is really a means to protect both the patient receiving the cells and the cells themselves. Your body tends to not like foreign objects shoved into it and the pouch in one respect protects the cells you are trying to put into the person. But you also want to be able to protect the person, and that means knowing where the cells are and having a means to remove them if you need to. That’s why it’s good to have a pouch that you can put in the body, take it out if you need, and replace if needed.”

Dr. Wei says it’s a little like making tea with a tea bag. When the need arises the pouch can secrete insulin but it does so in a carefully controlled manner.

“These are living cells and they are responsive, it’s not medicine where you can overdose, these cells are by nature self-regulating.”

They have already tested their approach with a variety of different kinds of islets, in a variety of different kinds of model.

“We’ve tested for insulin production, glucose stimulation and insulin response. We have tested them in a number of animal models and those studies are supporting our submission for a first-in-human safety clinical trial.”

Dr. Wei says if this approach works it could be used for other metabolic conditions such as parathyroid disorders. And she says a lot of this might not be possible without the early funding and support from CIRM.

“CIRM had the foresight to invest in groups that are looking ahead and said it would be great to have renewable cells to transplant into the body  (that function properly. We are grateful that groundwork that has been laid and are looking forward to advancing this work.”

And we are looking forward to working with them to help advance that work too.

Celebrating a young life that almost wasn’t

Often on the Stem Cellar we feature CIRM-funded work that is helping advance the field, unlocking some of the secrets of stem cells and how best to use them to develop promising therapies. But every once in a while it’s good to remind ourselves that this work, while it may often seem slow, is already saving lives.

Meet Ja’Ceon Golden. He was one of the first patients treated at U.C. San Francisco, in partnership with St. Jude Children’s Hospital in Memphis, as part of a CIRM-funded study to treat a rare but fatal disorder called Severe Combined Immunodeficiency (SCID). Ja’Ceon was born without a functioning immune system, so even a simple cold could have been fatal.

At UCSF a team led by Dr. Mort Cowan, took blood stem cells from Ja’Ceon and sent them to St. Jude where another team corrected the genetic mutation that causes SCID. The cells were then returned to UCSF and re-infused into Ja’Ceon.  

Over the next few months those blood stem cells grew in number and eventually helped heal his immune system.

He recently came back to UCSF for more tests, just to make sure everything is OK. With him, as she has been since his birth, was his aunt and guardian Dannie Hawkins. She says Ja’Ceon is doing just fine, that he has just started pre-K, is about to turn five years old and in January will be five years post-therapy. Effectively, Ja’Ceon is cured.

SCID is a rare disease, there are only around 70 cases in the US every year, but CIRM funding has helped produce cures for around 60 kids so far. A recent study in the New England Journal of Medicine showed that a UCLA approach cured 95 percent of the children treated.

The numbers are impressive. But not nearly as impressive, or as persuasive of the power of regenerative medicine, as Ja’Ceon and Dannie’s smiles.

Ja’Ceon on his first day at pre-K. He loved it.

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.

Gene therapy is life-changing for children with a life-threatening brain disorder

If you have never heard of AADC deficiency count yourself lucky. It’s a rare, incurable condition that affects only around 135 children worldwide but it’s impact on those children and their families is devastating. The children can’t speak, can’t feed themselves or hold up their head, they have severe mood swings and often suffer from insomnia.

But Dr. Krystof Bankiewicz, a doctor and researcher at the University of California San Francisco (UCSF), is using techniques he developed treating Parkinson’s disease to help those children. Full disclosure here, CIRM is funding Dr. Bankiewicz’s Parkinson’s clinical trial.

In AADC deficiency the children lack a critical enzyme that helps the brain make serotonin and dopamine, so called “chemical messengers” that help the cells in the brain communicate with each other. In his AADC clinical trial Dr. Bankiewicz and his team created a tiny opening in the skull and then inserted a functional copy of the AADC gene into two regions of the brain thought to have most benefit – the substantia nigra and ventral tegmental area of the brainstem.

Image showing target areas for AADC gene insertion: Courtesy UCSF

When the clinical trial began none of the seven children were able to sit up on their own, only two had any ability to control their head movement and just one could grasp an object in their hands. Six of the seven were described as moody or irritable and six suffered from insomnia.

In a news release Dr. Bankiewicz says the impact of the gene therapy was quite impressive: “Remarkably, these episodes were the first to disappear and they never returned. In the months that followed, many patients experienced life-changing improvements. Not only did they begin laughing and have improved mood, but some were able to start speaking and even walking.”

Those weren’t the only improvements, at the end of one year:

  • All seven children had better control of their head and body.
  • Four of the children were able to sit up by themselves.
  • Three patients could grasp and hold objects.
  • Two were able to walk with some support.

Two and a half years after the surgery:

  • One child was able to walk without any support.
  • One child could speak with a vocabulary of 50 words.
  • One child could communicate using an assistive device.

The parents also reported big improvements in mood and ability to sleep.

UCSF posted some videos of the children before and after the surgery and you can see for yourself the big difference in the children. It’s not a cure, but for families that had nothing in the past, it is a true gift.

The study is published in the journal Nature Communications.

A new way to evade immune rejection in transplanting cells

Immune fluorescence of HIP cardiomyocytes in a dish; Photo courtesy of UCSF

Transplanting cells or an entire organ from one person to another can be lifesaving but it comes with a cost. To avoid the recipient’s body rejecting the cells or organ the patient has to be given powerful immunosuppressive medications. Those medications weaken the immune system and increase the risk of infections. But now a team at the University of California San Francisco (UCSF) have used a new kind of stem cell to find a way around that problem.

The cells are called HIP cells and they are a specially engineered form of induced pluripotent stem cell (iPSC). Those are cells that can be turned into any kind of cell in the body. These have been gene edited to make them a kind of “universal stem cell” meaning they are not recognized by the immune system and so won’t be rejected by the body.

The UCSF team tested these cells by transplanting them into three different kinds of mice that had a major disease; peripheral artery disease; chronic obstructive pulmonary disease; and heart failure.

The results, published in the journal Proceedings of the National Academy of Science, showed that the cells could help reduce the incidence of peripheral artery disease in the mice’s back legs, prevent the development of a specific form of lung disease, and reduce the risk of heart failure after a heart attack.

In a news release, Dr. Tobias Deuse, the first author of the study, says this has great potential for people. “We showed that immune-engineered HIP cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals. This immune evasion was maintained in diseased tissue and tissue with poor blood supply without the use of any immunosuppressive drugs.”

Deuse says if this does work in people it may not only be of great medical value, it may also come with a decent price tag, which could be particularly important for diseases that affect millions worldwide.

“In order for a therapeutic to have a broad impact, it needs to be affordable. That’s why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases.”

Heads or tails? Stem cells help guide the decision

Two cell embryo

There are many unknown elements for what triggers the cells in an embryo to start dividing and multiplying and becoming every single cell in the body. Now researchers at the Gladstone Institutes in San Francisco have uncovered one of those elements, how embryos determine which cells become the head and which the tail.

In this CIRM-funded study the Gladstone team, led by Dr. Todd McDevitt, discovered almost by chance how the cells align in a heads-to-tail arrangement.

Todd McDevitt

They had created an organoid made from brain cells when they noticed that some of the cells were beginning to gather in an elongated fashion, in the same way that spinal cords do in a developing fetus.

In a news article, Nick Elder, a graduate student at Gladstone and the co-author of the study, published in the journal Development, says this was not what they had anticipated would happen: “Organoids don’t typically have head-tail directionality, and we didn’t originally set out to create an elongating organoid, so the fact that we saw this at all was very surprising.”

Further study enabled the team to identify which molecules were involved in signaling specific genes to switch on and off. These were similar to the process previously identified in developing mouse embryos.

“This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,” says McDevitt.

This is not just of academic interest either, it could have real world implications in helping understand what causes miscarriages or birth defects.

“We can use this organoid to get at unresolved human developmental questions in a way that doesn’t involve human embryos,” says Dr. Ashley Libby, another member of the team. “For instance, you could add chemicals or toxins that a pregnant woman might be exposed to, and see how they affect the development of the spinal cord.”