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

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

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.

200 years later, the search for a cure for Parkinson’s continues

On the surface, actor Michael J. Fox, singer Neil Diamond, civil rights activist Jesse Jackson and Scottish comedian Billy Connolly would appear to have little in common. Except for one thing. They all have Parkinson’s Disease (PD).

Their celebrity status has helped raise public awareness about the condition, but studies show that awareness doesn’t amount to an understanding of PD or the extent to which it impacts someone’s life. In fact a study in the UK found that many people still don’t think PD is a serious condition.

To try and help change that people around the world will be holding events today, April 11th, World Parkinson’s Day.

The disease was first described by James Parkinson in 1817 in “An Essay on the Shaking Palsy”. In the essay Parkinson described a pattern of trembling in the hands and fingers, slower movement and loss of balance. Our knowledge about the disease has advanced in the last 200 years and now there are treatments that can help slow down the progression of the disease. But those treatments only last for a while, and so there is a real need for new treatments.  

That’s what Jun Takahashi’s team at Kyoto University in Japan hope to provide. In a first-of-its-kind procedure they took skin cells from a healthy donor and reprogrammed them to become induced pluripotent stem cells (iPSCs), or stem cells that become any type of cell. These iPSCs were then turned into the precursors of dopamine-producing neurons, the cells destroyed by PD, and implanted into 12 brain regions known to be hotspots for dopamine production.

The procedure was carried out in October and the patient, a male in his 50s, is still healthy. If his symptoms continue to improve and he doesn’t experience any bad side effects, he will receive a second dose of dopamine-producing stem cells. Six other patients are scheduled to receive this same treatment.

Earlier tests in monkeys showed that the implanted stem cells improved Parkinson’s symptoms without causing any serious side effects.

Dompaminergic neurons derived from stem cells

Scientists at UC San Francisco are trying a different approach, using gene therapy to tackle one of the most widely recognized symptoms of PD, muscle movement.

In the study, published in the journal Annals of Neurology, the team used an inactive virus to deliver a gene to boost production of dopamine in the brain. In a Phase 1 clinical trial 15 patients, whose medication was no longer able to fully control their movement disorder, were treated with this approach. Not only were they able to reduce their medication – up to 42 percent in some cases – the medication they did take lasted longer before causing dyskinesia, an involuntary muscle movement that is a common side effect of the PD medication.

In a news article Dr. Chad Christine, the first author of the study, says this approach may also help reduce other symptoms.

“Since many patients were able to substantially reduce the amount of Parkinson’s medications, this gene therapy treatment may also help patients by reducing dose-dependent side effects, such as sleepiness and nausea.” 

At CIRM we have a long history of funding research into PD. Over the years we have invested more than $55 million to try and develop new treatments for the disease.

In June 2018, the CIRM Board awarded $5.8 million to UC San Francisco’s Krystof Bankiewicz and Cedars-Sinai’s Clive Svendsen. They are using neural progenitor cells, which have the ability to multiply and turn into other kinds of brain cells, and engineering them to express the growth factor GDNF which is known to protect the cells damaged in PD. The hope is that when transplanted into the brain of someone with PD, it will help slow down, or even halt the progression of the disease. 

The CIRM funding will hopefully help the team do the pre-clinical research needed to get the FDA’s go-ahead to test this approach in a clinical trial. 

David Higgins, CIRM Board member and Patient Advocate for Parkinson’s Disease

At the time of the award David Higgins, PhD, the CIRM Board Patient Advocate for Parkinson’s Disease, said: “One of the big frustrations for people with Parkinson’s, and their families and loved ones, is that existing therapies only address the symptoms and do little to slow down or even reverse the progress of the disease. That’s why it’s important to support any project that has the potential to address Parkinson’s at a much deeper, longer-lasting level.”

But we don’t just fund the research, we try to bring the scientific community together to help identify obstacles and overcome them. In March of 2013, in collaboration with the Center for Regenerative Medicine (CRM) of the National Institutes of Health (NIH), we held a two-day workshop on cell therapies for Parkinson’s Disease. The experts outlined the steps needed to help bring the most promising research to patients.

Around one million Americans are currently living with Parkinson’s Disease. Worldwide the number is more than ten million. Those numbers are only expected to increase as the population ages. There is clearly a huge need to develop new treatments and, hopefully one day, a cure.

Till then days like April 11th will be an opportunity to remind ourselves why this work is so important.

Stem Cells make the cover of National Geographic

clive & sam

Clive Svendsen, PhD, left, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and Samuel Sances, PhD, a postdoctoral fellow at the institute, with the January 2019 special edition of National Geographic. The magazine cover features a striking image of spinal cord tissue that was shot by Sances in his lab. Photo by Cedars-Sinai.

National Geographic is one of those iconic magazines that everyone knows about but few people read. Which is a shame, because it’s been around since 1888 and has helped make generations of readers aware about the world around them. And now, it’s shifting gears and helping people know more about the world inside them. That’s because a special January edition of National Geographic highlights stem cells.

The issue, called ‘The Future of Medicine’, covers a wide range of issues including stem cell research being done at Cedars-Sinai by Clive Svendsen and his team (CIRM is funding Dr. Svendsen’s work in a clinical trial targeting ALS, you can read about that here). The team is using stem cells and so-called Organ-Chips to develop personalized treatments for individual patients.

Here’s how it works. Scientists take blood or skin cells from individual patients, then using the iPSC method, turn those into the kind of cell in the body that is diseased or damaged. Those cells are then placed inside a device the size of an AA battery where they can be tested against lots of different drugs or compounds to see which ones might help treat that particular problem.

This approach is still in the development phase but if it works it would enable doctors to tailor a treatment to a patient’s specific DNA profile, reducing the risk of complications and, hopefully, increasing the risk it will be successful. Dr. Svendsen says it may sound like science fiction, but this is not far away from being science fact.

“I think we’re entering a new era of medicine—precision medicine. In the future, you’ll have your iPSC line made, generate the cell type in your body that is sick and put it on a chip to understand more about how to treat your disease.”

Dr. Svendsen isn’t the only connection CIRM has to the article. The cover photo for the issue was taken by Sam Sances, PhD, who received a CIRM stem cell research scholarship in 2010-2011. Sam says he’s grateful to CIRM for being a longtime supporter of his work. But then why wouldn’t we be. Sam – who is still just 31 years old – is clearly someone to watch. He got his first research job, as an experimental coordinator, with Pacific Ag Research in San Luis Obispo when he was still in high school.

 

 

 

 

 

 

A stepping stone for bringing stem cell therapy to patients with ALS

ALS Picture1

Imagine being told that you have a condition that gradually causes you to lose the ability to control your body movements, from picking up a pencil to walking to even breathing. Such is the reality for the nearly 6,000 people who are diagnosed with amyotrophic lateral sclerosis (ALS) every year, in the United States alone.

ALS, also known as Lou Gehrig’s disease, is a neurodegenerative disease that causes the degradation of motor neurons, or nerves that are responsible for all voluntary muscle movements, like the ones mentioned above. It is a truly devastating disease with a particularly poor prognosis of two to five years from the time of diagnosis to death. There are only two approved drugs for ALS and these do not stop it but only slow progression of the disease; and even then only for some patients, not all.

A ray of hope for such a bleak treatment landscape, has been the advent of stem cell therapy options over the past decade. Of particular excitement is the recent discovery made Nasser Aghdami’s group at the Royan Institute for Stem Cell Biology and Technology in Iran.

Two small Phase I clinical trials detailed in Cell Journal demonstrated that injecting mesenchymal stem cells (MSCs), derived from the patient’s own bone marrow, was safe when administered via injection into the bloodstream or the spinal cord. Previous studies had shown that MSCs both revived motor neurons and extended the lifespan in a rodent model of the disease.

In humans, many studies have shown that MSCs taken from bone marrow are safe for use in humans, but these studies have disagreed about whether injection via the bloodstream or spinal cord route is the most effective way to deliver the therapy. This report confirms that both routes of administration are safe as no adverse clinical events were observed for either group throughout the study time frame.

While an important stepping stone, there is still a long way to go. For example, while no adverse clinical events were observed in either group, the overall ALS-FRS score, a clinical scale to determine ALS disease progression, worsened in all patients over the course of the study. Whether this was just due to natural progression of the disease, or because of the stem cell treatment is difficult to determine given the small size of the cohort.

One reason the scientists suggest that could explain the disease decline is because the MSCs were taken from the ALS patients themselves, which means these cells were likely not functioning optimally prior to re-introduction into the patient. To remedy this, they hope to test the effect of MSCs taken from healthy donors in both injection routes in the future. They also need a larger cohort of patients to determine whether or not there is a difference in the therapeutic effect of administering stem cells via the two different routes.

While it may seem that the results from this clinical trial are not particularly groundbreaking or innovative, it is important to remember that these incremental improvements through clinical trials are critical for bringing safe and effective therapies to the market. For more information on the different phases of clinical trials, please refer to this video.

CIRM is also funding clinical trials targeting ALS. One is a Phase 1 trial out of Cedars-Sinai Medical Center and another is a Phase 3 trial with the company Brainstorm Cell Therapeutics.

ALS is in the spotlight in CIRM’s “Ask the Expert About ALS & Stem Cells” Facebook Live event

The Catch

San Francisco 49ers Dwight Clark makes his iconic “Catch” against the Dallas Cowboys

American Football great Dwight Clark was renowned for having the safest hands in the game when he played for the San Francisco 49ers. But in September 2015 he was diagnosed with ALS (also known as Lou Gehrig’s disease) after not being able to use those hands to open a package of sugar. Less than three years later he was dead.

Amyotrophic lateral sclerosis – ALS’ formal title – is a nasty disease that relentlessly destroys the nerve cells in the brain and spinal cord that control movement and breathing. It is always fatal. There are only two drugs approved for ALS and they don’t work for most people. There is no cure.

AskExpertsALSJUL2018

That’s why CIRM chose ALS to be the subject of its latest Facebook Live Ask the Expert event (click here for the event’s FaceBook Live page). There’s a real need for new approaches to help people battling this deadly condition. And CIRM is funding two clinical trials that hope to do just that.

This Ask the Expert event will feature Clive Svendsen, PhD, Director of Cedars-Sinai’s Board of Governors Regenerative Medicine Institute, and Robert Baloh, MD, PhD, Director of Neuromuscular Medicine at Cedars-Sinai. They’ll be joined by Ralph Kern, MD, Chief Operating Officer and Chief Medical Officer at  BrainStorm Cell Therapeutics. The panel will be completed by CIRM Senior Science Officer Lila Collins.

The four will discuss the clinical trials that CIRM is funding with Cedars-Sinai and BrainStorm, and look at other promising research taking place.

Ask the Experts About ALS and Stem Cells is an opportunity for everyone in the ALS community to hear about the very latest in stem cell research targeting this devastating disease,” Svendsen said. “There has recently been some progress in the search for new treatments, which has energized all of us looking for effective therapies—and one day, a cure.”

Because Facebook Live is an interactive event people will be able to post comments and ask questions of the experts.

Dr. Baloh says we are now at a crucial time in the search for new approaches to help people with ALS.

“Many researchers believe that stem cells and gene therapies hold great promise for finding effective treatments, and more trials are needed to explore that potential.”

Our Facebook Live event, “Ask the Experts About ALS and Stem Cells” is tomorrow – Tuesday, July 31st – from noon till 1pm PST. You can join us by logging on to Facebook and going to the FaceBook Live broadcast link at: https://bit.ly/2uYQ8wM

Also, make sure to “like” our FaceBook page before the event to receive a notification when we’ve gone live for this and future events.

We want to hear from you, so you will be able to post questions in real-time for the experts to answer or, you can email them directly to us beforehand at info@cirm.ca.gov

If you miss the event, not to worry. A recording of the session will be available in our FaceBook videos page shortly after the broadcast ends.

We look forward to seeing you there.

 

Meet the high school student who moonlights as a neuroscientist

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students. Today, you’ll read about one of our former SPARK high school students.


Emma Friedenberg and former CIRM SPARK Director Karen Ring at the 2017 SPARK Conference.

Emma Friedenberg is a high school senior at Campbell Hall in North Hollywood, California. She’s also an up-and-coming neuroscientist who has her sights set on unraveling the complexities of the brain and discovering cures for degenerative brain diseases. Emma spent the summer of 2017 studying Huntington’s disease in the lab of Dr. Virginia Mattis at the Cedars-Sinai Medical Center. Her internship was possible because of the CIRM SPARK high school educational program which gives California students the opportunity to do stem cell research for a summer.

Below is an interview with Emma about her SPARK experience and how the program is helping her pursue her passions for research and medicine.

Q: How did you learn about the CIRM SPARK program and why did you want to apply?

I’ve been a clinical volunteer at Cedars-Sinai Medical Center for two years in the Intensive Care Unit and the Neurology and Spine Unit. I was submitting my application to return as a volunteer when I explored Cedars-Sinai’s Outreach website page and found the CIRM SPARK program. I knew immediately it was a perfect fit. I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon. The CIRM SPARK program at Cedars within the Board of Governor’s Regenerative Medicine Institute had an option to be involved specifically in the Brain Program. In Dr. Virginia Mattis’ lab, I studied translational stem cell therapies for neurodegenerative diseases, in particular Huntington’s Disease. As Cedars-Sinai calls it, a “bench to bedside” approach is an unparalleled and invaluable experience and huge advantage in science.

Q: What was your SPARK research project?

At Cedars-Sinai, I was mentored by Dr. Virginia Mattis in her stem cell lab. The Mattis Lab researches stem cell therapies for Huntington’s disease (HD), a neurodegenerative brain disease. HD is caused by a loss of neurons, specifically medium spiny neurons in the striatum of Huntington’s patients. We used induced pluripotent stem cells to model HD in a petri dish to study the development of the disease and to create medium spiny neurons that could one day be transplanted into Huntington’s patients to replace lost and damaged cells.

Medium spiny neurons made from Huntington’s disease patient induced pluripotent stem cells. (Image credit: Mattis Lab, Cedars Sinai)

My primary research in the Mattis Lab was experimenting on our cell line to find the most time and cost-effective procedure to produce large populations of medium spiny neurons, because current methods are expensive and largely inefficient. However, my internship was not limited to the laboratory. I spent a significant amount of time shadowing doctors in the ALS Clinic.

Q: What was your experience in the CIRM SPARK program like?

In one word, the CIRM SPARK program was incredible –a one of a kind opportunity. The sciences are my personal passion and the cornerstone of my academic pursuits. The CIRM SPARK program has bolstered my scientific knowledge and provided practical experience in a real-world laboratory environment. A career in medicine is a significant commitment, and I’m confident the CIRM SPARK program was a beneficial start to obtaining my goals.

Cedars-Sinai SPARK students celebrating the completion of their 2017 internships.

Q: What do you value most about your SPARK experience?

It was wonderful to be part of a program which understood collaboration and offered a plethora of learning opportunities outside of the wet lab. What I will keep with me is not only techniques of immunocytochemistry and microscopy, but also the advice and encouragement from accomplished scientists like Clive Svendsen and my mentor Virginia Mattis.

Q: What are your future goals?

I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon.

Q: Who is your scientific idol and why?

I recently read Dr. Eric Kandel’s book, The Age of Insight: The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present. Dr. Kandel is a neuroscientist and a Professor at Columbia University. He received the Nobel Prize for his work in memory storage using Aplysia, a type of sea slug. His book examines how the human brain responds to art. What I find so inspiring about his book is his interdisciplinary approach to science, a combination of neuroscience, psychoanalysis, biology, and art. The human brain is so complicated that it can be studied from numerous perspectives, from biology to chemistry to electrophysiology. It is not until we can begin to merge these understandings that we will begin to unlock the secrets of the brain. Dr. Kandel is not only a scientist, but an intellectual.

Q: What is your favorite thing about being a scientist?

For centuries, the human brain was an anomaly, unexplainable by science. With 100 billion neurons and 100 trillion connections, the brain is the most complex network in the universe. How the brain functions as an information-processing organ and regulates emotion, behavior, and cognition as well as basic body functions like breathing remains a mystery. In recent years, there has been significant progress in brain research. Scientists are on the brink of major breakthroughs, but there is significant work to do particularly on neurological brain disorders. Being a scientist means living on the cutting-edge of human innovation. I enjoy being able to both ask and answer questions that will benefit humankind.


Related Links:

Tiny blood vessels in the brain can spur the growth of spinal motor neurons

Last week, researchers from Cedars-Sinai Medical Center added a new piece to the complex puzzle of what causes neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). The team discovered that the tiny blood vessels in our brains do more than provide nutrients to and remove waste products from our brain tissue. It turns out that these blood vessels can stimulate the growth of new nerve cells called spinal motor neurons, which directly connect to the muscles in our body and control how they move. The study, which was funded in part by a CIRM Discovery research-stage Inception award, was published in the journal Stem Cell Reports.

The Cedars team used a combination of human induced pluripotent stem cells (iPSCs) and organ-on-a-chip technology to model the cellular microenvironment of the spinal cord. They matured the iPSCs into both spinal motor progenitor cells and brain endothelial cells (which line the insides of blood vessels). These cells were transferred to an organ-chip where they were able to make direct contact and interact with each other.

Layers of spinal motor neuron cells (top, in blue) and capillary cells (bottom, in red) converge inside an Organ-Chip. Neurons and capillary cells interact together along the length of the chip. (Cedars-Sinai Board of Governors Regenerative Medicine Institute).

The researchers discovered that exposing the spinal motor progenitor cells to the blood vessel endothelial cells in these organ-chips activated the expression of genes that directed these progenitor cells to mature into spinal cord motor neurons.

Hundreds of spinal motor neurons spontaneously communicate through electrical signals inside an Organ-Chip. Neurons fire individually (flashing dots) and in synchronized bursts (bright waves). (Cedars-Sinai)

First author on the study, Samuel Sances, explained their findings in a news release:

“Until now, people thought these blood vessels just delivered nutrients and oxygen, removed waste and adjusted blood flow. We showed that beyond plumbing, they are genetically communicating with the neurons.”

The team also showed the power of stem cell-based organ-chip platforms for modeling diseases like ALS and answering key questions about why these diseases occur.

“What may go wrong in the spinal neurons that causes the motor neurons to die?” Sances asked. “If we can model an individual ALS patient’s tissues, we may be able to answer that question and one day rescue ALS patients’ neurons through new therapies.”

Clive Svendsen, a CIRM grantee and the senior author on the study, said that his team will conduct additional studies using organ-chip technology to study the interactions between iPSC-derived neurons and blood vessels of healthy individuals and ALS patients. Differences in these cellular interactions in diseased patient cells could offer new targets for developing ALS therapies.

The current study is a collaboration between Cedars and a Boston company called Emulate, Inc. Emulate developed the organ-chip technology and is collaborating with Svendsen at Cedars to not only model neurodegenerative diseases, but also model other organ systems. Be sure to check out our recent blog about their efforts to create a stem cell-based gut-on-a-chip, which they hope will pave the way for personalized treatments for patients with gastrointestinal diseases like Chrohn’s and inflammatory bowel disease.

Stem Cell Roundup: Improving muscle function in muscular dystrophy; Building a better brain; Boosting efficiency in making iPSC’s

Here are the stem cell stories that caught our eye this week.

Photos of the week

TGIF! We’re so excited that the weekend is here that we are sharing not one but TWO amazing stem cell photos of the week.

RMI IntestinalChip

Image caption: Cells of a human intestinal lining, after being placed in an Intestine-Chip, form intestinal folds as they do in the human body. (Photo credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute)

Photo #1 is borrowed from a blog we wrote earlier this week about a new stem cell-based path to personalized medicine. Scientists at Cedars-Sinai are collaborating with a company called Emulate to create intestines-on-a-chip using human stem cells. Their goal is to create 3D-organoids that represent the human gut, grow them on chips, and use these gut-chips to screen for precision medicines that could help patients with intestinal diseases. You can read more about this gut-tastic research here.

Young mouse heart 800x533

Image caption: UCLA scientists used four different fluorescent-colored proteins to determine the origin of cardiomyocytes in mice. (Image credit: UCLA Broad Stem Cell Research Center/Nature Communications)

Photo #2 is another beautiful fluorescent image, this time of a cross-section of a mouse heart. CIRM-funded scientists from UCLA Broad Stem Cell Research Center are tracking the fate of stem cells in the developing mouse heart in hopes of finding new insights that could lead to stem cell-based therapies for heart attack victims. Their research was published this week in the journal Nature Communications and you can read more about it in a UCLA news release.

Stem cell injection improves muscle function in muscular dystrophy mice

Another study by CIRM-funded Cedars-Sinai scientists came out this week in Stem Cell Reports. They discovered that they could improve muscle function in mice with muscular dystrophy by injecting cardiac progenitor cells into their hearts. The injected cells not only improved heart function in these mice, but also improved muscle function throughout their bodies. The effects were due to the release of microscopic vesicles called exosomes by the injected cells. These cells are currently being used in a CIRM-funded clinical trial by Capricor therapeutics for patients with Duchenne muscular dystrophy.

How to build a better brain (blob)

For years stem cell researchers have been looking for ways to create “mini brains”, to better understand how our own brains work and develop new ways to repair damage. So far, the best they have done is to create blobs, clusters of cells that resemble some parts of the brain. But now researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have come up with a new method they think can advance the field.

Their approach is explained in a fascinating article in the journal Science News, where lead researcher Bennet Novitch says finding the right method is like being a chef:

“It’s like making a cake: You have many different ways in which you can do it. There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”

Brain cake. Yum.

A more efficient way to make iPS cells

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Shinya Yamanaka. (Image source: Ko Sasaki, New York Times)

In 2006 Shinya Yamanaka discovered a way to take ordinary adult cells and reprogram them into embryonic-like stem cells that have the ability to turn into any other cell in the body. He called these cells induced pluripotent stem cells or iPSC’s. Since then researchers have been using these iPSC’s to try and develop new treatments for deadly diseases.

There’s been a big problem, however. Making these cells is really tricky and current methods are really inefficient. Out of a batch of, say, 1,000 cells sometimes only one or two are turned into iPSCs. Obviously, this slows down the pace of research.

Now researchers in Colorado have found a way they say dramatically improves on that. The team says it has to do with controlling the precise levels of reprogramming factors and microRNA and…. Well, you can read how they did it in a news release on Eurekalert.

 

 

 

Using heart stem cells to help boys battling a deadly disorder

 

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Caleb Sizemore, a young man with DMD, speaks to the CIRM Board about his treatment in the Capricor clinical trial.

It’s hard to imagine how missing just one tiny protein can have such a devastating impact on a person. But with Duchenne Muscular Dystrophy (DMD) the lack of a single protein called dystrophin has deadly consequences. Now a new study is offering hope we may be able to help people with this rare genetic disorder.

DMD is a muscle wasting condition that steadily destroys the muscles in the arms and legs, heart and respiratory system. It affects mostly boys and it starts early in life, sometimes as young as 3 years old, and never lets up. By early teens many boys are unable to walk and are in a wheelchair. Their heart and breathing are also affected. In the past most people with DMD didn’t survive their teens. Now it’s more common for them to live into their 20’s and 30’s, but not much beyond that.

Results from a clinical trial being run by Capricor Therapeutics – and funded by CIRM – suggest we may be able to halt, and even reverse, some of the impacts of DMD.

Capricor has developed a therapy called CAP-1002 using cells derived from heart stem cells, called cardiospheres. Boys and young men with DMD who were treated with CAP-1002 experienced what Capricor calls “significant and sustained improvements in cardiac structure and function, as well as skeletal muscle function.”

In a news release Dr. Ronald Victor, a researcher at Cedars-Sinai Heart Institute and the lead investigator for the trial, said they followed these patients for 12 months after treatment and the results are encouraging:

“Because Duchenne muscular dystrophy is a devastating, muscle-wasting disease that causes physical debilitation and eventually heart failure, the improvements in heart and skeletal muscle in those treated with a single dose of CAP-1002 are very promising and show that a subsequent trial is warranted. These early results provide hope for the Duchenne community, which is in urgent need of a major therapeutic breakthrough.”

According to the 12-month results:

  • 89 percent of patients treated with CAP-1002 showed sustained or improved muscle function compared to untreated patients
  • The CAP-1002 group had improved heart muscle function compared to the untreated group
  • The CAP-1002 group had reduced scarring on their heart compared to the untreated group.

Now, these results are still very early stage and there’s a danger in reading too much into them. However, the fact that they are sustained over one year is a promising sign. Also, none of the treated patients experienced any serious side effects from the therapy.

The team at Capricor now plans to go back to the US Food and Drug Administration (FDA) to get clearance to launch an even larger study in 2018.

For a condition like DMD, that has no cure and where treatments can simply slow down the progression of the disorder, this is a hopeful start.

Caleb Sizemore is one of the people treated in this trial. You can read his story and listen to him describing the impact of the treatment on his life.