CIRM Board Approves Two Discovery Research Projects for COVID-19

Dr. Steven Dowdy (left), Dr. Evan Snyder (center), and Dr. John Zaia (right)

This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two additional discovery research projects as part of the $5 million in emergency funding for COVID-19 related projects.  This brings the number of COVID-19 projects CIRM is supporting to 15, including three clinical trials.

The Board awarded $249,999 to Dr. Evan Snyder at the Sanford Burnham Prebys Medical Discovery Institute.  The study will use induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids.  These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treatment of the virus. The iPSCs and the subsequent lung organoids created will reflect diversity by including male and female patients from the Caucasian, African-American, and Latinx population.

This award is part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.

The Board also awarded $150,000 to Dr. Steven Dowdy at UC San Diego for development of another potential treatment for COVID-19.  

Dr. Dowdy and his team are working on developing a new, and hopefully more effective, way of delivering a genetic medicine, called siRNA, into the lungs of infected patients. In the past trying to do this proved problematic as the siRNA did not reach the appropriate compartment in the cell to become effective. However, the team will use an iPSC lung model to help them identify ways past this barrier so the siRNA can attack the virus and stop it replicating and spreading throughout the lungs.

This award is part of CIRM’s Inception Awards Program (DISC1), which supports transformational ideas that require the generation of additional data.

A supplemental award of $250,000 was approved for Dr. John Zaia at City of Hope to continue support of a CIRM funded clinical study that is using convalescent plasma to treat COVID-19 patients.  The team recently launched a website to enroll patients, recruit plasma donors, and help physicians enroll their patients.

“The use of induced pluripotent stem cells has expanded the potential for personalized medicine,” says Dr. Maria T. Millan, the President & CEO of CIRM. “Using patient derived cells has enabled researchers to develop lung organoids and lung specific cells to test numerous COVID-19 therapies.”

Stem cells used to look at how COVID-19 attacks heart muscle

Human induced pluripotent stem cell-derived cardiomyocytes (heart cells) shown in green and blue, are infected by the novel coronavirus SARS-CoV-2 (red). Image provided by Cedars-Sinai Board of Governors Regenerative Medicine Institute.

There is still a lot that we don’t understand about SARS-CoV-2 (COVID-19), the new coronavirus that has caused a worldwide pandemic. Some patients that contract the virus experiences heart problems, but the reasons are not entirely clear. Pre-existing heart conditions or inflammation and oxygen deprivation that result from COVID-19 have all been implicated but more evidence needs to be collected.

To evaluate this, a joint study between Cedars-Sinai Board of Governors Regenerative Medicine Institute and the UCLA Broad Stem Cell Research Center used human induced pluripotent stem cells (iPSCs), a kind of stem cell that can become any kind of cell in the body and is usually made from skin cells. The iPSCS were converted into heart cells and infected with COVID-19 in order to study the effects of the virus.

The results of this study showed that the iPSC-derived heart cells are susceptible to COVID-19 infection and that the virus can quickly divide inside the heart cells. Furthermore, the infected heart cells showed changes in their ability to beat 72 hours after infection.

In a press release, Dr. Clive Svendsen, senior and co-corresponding author of the study and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, elaborated on the results.

“This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmias, heart failure and viral myocarditis. While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID-19.”

Although this study does not perfectly replicate the conditions inside the human body, the iPSC heart cells may also help identify and screen new potential drugs that could alleviate viral infection of the heart.

The research team has already found that treatment with an antibody called ACE2 was able to decrease viral replication on the iPSC heart cells.

In the same press release Dr. Arun Sharma, first author and another co-corresponding author of the study and a research fellow at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, had this to say about the ACE2 antibody.

“By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell. This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection.”

The study’s third co-corresponding author was Dr. Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

The full results of this study were published in Cell Reports Medicine.

CIRM Board Approves Third Clinical Trial for COVID-19

Dr. Xiaokui Zhang (left), Dr. Albert Wong (center), and Dr. Preet Chaudhary (right)

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $750,000 to Dr. Xiaokui Zhang at Celularity to conduct a clinical trial for the treatment of COVID-19.  This brings the total number of CIRM clinical trials to 64, including three targeting the coronavirus.

This trial will use blood stem cells obtained from the placenta to generate natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, and administer them to patients with COVID-19.  NK cells play an important role in defense against cancer and in fighting off viral infections.  The goal is to administer these cells to locate the active sites of COVID-19 infection and destroy the virus-infected cells.  These NK cells have been used in two other clinical trials for acute myeloid leukemia and multiple myeloma.

The Board also approved two additional awards for Discovery Stage Research (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.

One award for $100,000 was given to Dr. Albert Wong at Stanford.  Dr. Wong has recently received an award from CIRM to develop a vaccine that produces a CD8+ T cell response to boost the body’s immune response to remove COVID-19 infected cells.  The current award will enable him to expand on the initial approach to increase its potential to impact the Latinx and African American populations, two ethnicities that are disproportionately impacted by the virus in California.

The other award was for $249,996 and was given to Dr. Preet Chaudhary at the University of Southern California.  Dr. Chaudary will use induced pluripotent stem cells (iPSCs) to generate natural killer cells (NK). These NK cells will express a chimeric antigen receptor (CAR), a synthetic receptor that will directly target the immune cells to kill cells infected with the virus.  The ultimate goal is for these iPSC-NK-CAR cells to be used as a treatment for COVID-19. 

“These programs address the role of the body’s immune T and NK cells in combatting viral infection and CIRM is fortunate enough to be able to assist these investigators in applying experience and knowledge gained elsewhere to find targeted treatments for COVID-19” says Dr. Maria T. Millan, the President & CEO of CIRM. “This type of critical thinking reflects the resourcefulness of researchers when evaluating their scientific tool kits.  Projects like these align with CIRM’s track record of supporting research at different stages and for different diseases than the original target.”

The CIRM Board voted to endorse a new initiative to refund the agency and provide it with $5.5 billion to continue its work. The ‘California Stem Cell Research, Treatments and Cures Initiative of 2020 will appear on the November ballot. 

The Board also approved a resolution honoring Ken Burtis, PhD., for his long service on the Board. Dr. Burtis was honored for his almost four decades of service at UC Davis as a student, professor and administrator and for his 11 years on the CIRM Board as both a member and alternate member. In the resolution marking his retirement the Board praised him, saying “his experience, commitment, knowledge, and leadership, contributed greatly to the momentum of discovery and the future therapies which will be the ultimate outcome of the dedicated work of the researchers receiving CIRM funding.”

Jonathan Thomas, the Chair of the Board, said “Ken has been invaluable and I’ve always found him to have tremendous insight. He has served as a great source of advice and inspiration to me and to the ICOC in dealing with all the topics we have had to face.” 

Lauren Miller Rogen thanked Dr. Burtis, saying “I sat next to you at my first meeting and was feeling so extraordinarily overwhelmed and you went out of your way to explain all these big science words to me. You were always a source of help and support, and you explained things to me in a way that I always appreciated with my normal brain.”

Dr. Burtis said it has been a real honor and privilege to be on the Board. “I’ve been amazed and astounded at the passion and dedication that the Board and CIRM staff have brought to this work. Every meeting over the years there has been a moment of drama and then resolution and this Board always manages to reach agreement and serve the people of California.”

Stem cells used to promote quick and precise bone healing

A close-up view of the intricate microarchitecture of the pluripotent stem-cell-derived extracellular matrix. Image Credit: Carl Gregory/Texas A&M

Although some broken bones can be mended with the help of a cast, others require more complex treatments. Bone grafts, which can come from the patient’s own body or a donor, are used to transplant bone tissue to the injury site. However, these procedures can have setbacks such as increased recovery time and chronic pain. Each year approximately 600,000 people in the United States alone experience complications from bone healing.

Researchers at Texas A&M University found a way to use induced pluripotent stem cells (iPSCs), a type of stem cell that can turn into any cell type and can be derived from adults cells (e.g. skin cells), to create superior bone grafts. The team of researchers said these grafts could potentially be used to promote swift and precise bone healing, enabling patients to optimally benefit from surgical intervention.

The Texas A&M team used iPSCS to make mesenchymal stem cells (MSCs), which make the extracellular matrix needed for bone grafts. MSCs can be obtained from bone marrow, but they have a relatively shorter life span and are not as biologically active when compared to MSCs generated from iPSCs.

To test the effectiveness of their iPSC generated bone grafts, they implanted the extracellular matrix at a site of bone defects. After a few weeks, they found that their iPSC generated matrix was five to sixfold more effective than the best FDA-approved graft stimulator.

In a news release from Texas A&M, Dr. Roland Kaunas discusses the potential benefits of using iPSC generated bone grafts.

“Our material is very promising because the pluripotent stem cells can ideally generate many batches of the extracellular matrix from just a single donor which will greatly simplify the large-scale manufacturing of these bone grafts.”

Additionally, the Texas A&M team said this approach has the potential to be incorporated into numerous engineered implants, such as 3D-printed implants or metal screws, so that these parts integrate better with the surrounding bone.

The full results of this study were published in Nature Communications.

A brief video on bone grafts from Texas A&M is available below.

“Mini” human liver made of stem cells successfully transplanted in rats

Miniature liver made from human skin cells turned stem cells turned specialized liver cells Photo Credit: University of Pittsburgh School of Medicine

According to the American Liver Foundation website, almost 14,000 patients are on the waiting list for a liver transplant. But what if there was a way to generate a liver using your own cells so that you didn’t have to wait? Researchers at the University of Pittsburgh School of Medicine have gotten one step closer towards that goal.

Using human skin cells from volunteers, Dr. Alejandro Soto-Gutierrez and his team of researchers were able to create “mini” livers which were successfully transplanted into rats. In this proof of concept experiment, the “mini” livers survived inside the rats for four days. Additionally, they secreted bile acids and urea and produced proteins similar to a normal liver. Normally, liver maturation takes up to two years in a natural environment, but Dr. Soto-Gutierrez and his team were able to do this in under a month.

The researchers were able to do this by taking human skin cells and reprogramming them into induced pluripotent stem cells (iPSCs), a type of stem cell that has the ability to turn into virtually any other kind of cell. These newly formed iPSCs were then made into liver cells which were then seeded into a rat liver with all of its own cells removed. These newly formed “mini” livers were then transplanted into the rats.

In a press release, Dr. Soto-Gutierrez discusses what it was like observing the newly created “mini” livers.

“Seeing that little human organ there inside the animal – brown, looking like a liver – that was pretty cool. This thing that looks like a liver and functions like a liver came from somebody’s skin cells.”

Although these results were promising, there are still challenges that need to be addressed in future studies such as long-term survival and safety issues.

Even so, Dr. Soto-Gutierrez says his research could one-day benefit patients who are running out of options.

“The long-term goal is to create organs that can replace organ donation, but in the near future, I see this as a bridge to transplant. For instance, in acute liver failure, you might just need hepatic boost for a while instead of a whole new liver”.

The full results to this study were published in Cell Reports.

What to be thankful for this Thanksgiving: scientists hard at work

Biomedical technician Louis Pinedo feeds stem cells their special diet. Photo by Cedars-Sinai.

With Thanksgiving and Black Friday approaching in the next couple of days, we wanted to give thanks to all the scientists hard at work during this holiday weekend. Science does not sleep–the groundbreaking research and experiments that are being conducted do not take days off. There are tasks in the laboratory that need to be done daily otherwise months, even years, of important work can be lost in an instant.

Below is a story from Cedars-Sinai Medical Center that talks about one of these scientists, Louis Pinedo, that will be working during this holiday weekend.

Stem Cells Don’t Take the Day Off on Thanksgiving

Inside a Cedars-Sinai Laboratory, Where a Scientist Will be Busy Feeding Stem Cells During the Holiday

While most of us are stuffing ourselves with turkey and pumpkin pie at home on Thanksgiving Day, the staff at one Cedars-Sinai laboratory will be on the job, feeding stem cells.

“Stem cells do not observe national holidays,” says Loren Ornelas-Menendez, the manager of a lab that converts samples of adult skin and blood cells into stem cells—the amazing “factories” our bodies use to make our cells. These special cells help medical scientists learn how diseases develop and how they might be cured.

Stem cells are living creatures that must be hand-fed a special formula each day, monitored for defects and maintained at just the right temperature. And that means the cell lab is staffed every day, 52 weeks a year.

These cells are so needy that Ornelas-Menendez jokes: “Many people have dogs. We have stem cells.”

Millions of living stem cells are stored in the David and Janet Polak Foundation Stem Cell Core Laboratory at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. Derived from hundreds of healthy donors and patients, they represent a catalogue of human ills, including diabetes, breast cancer, Alzheimer’s disease, Parkinson’s disease and Crohn’s disease.

Cedars-Sinai scientists rely on stem cells for many tasks: to make important discoveries about how our brains develop; to grow tiny versions of human tissues for research; and to create experimental treatments for blindness and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) that they are testing in clinical trials.

The lab’s main collection consists of induced pluripotent stem cells, or iPSCs, which mimic the all-powerful stem cells we all had as embryos. These ingenious cells, which Cedars-Sinai scientists genetically engineer from adult cells, can make any type of cell in the body—each one matching the DNA of the donor. Other types of stem cells in the lab make only one or two kinds of cells, such as brain or intestinal cells.

Handy and versatile as they are, stem cells are high-maintenance. A few types, such as those that make connective tissue cells for wound healing, can be fed as infrequently as every few days. But iPSCs require a daily meal to stay alive, plus daily culling to weed out cells that have started to turn into cells of the gut, brain, breast or other unwanted tissues.

So each day, lab staff suit up and remove trays of stem cells from incubators that are set at a cozy 98.6 degrees. Peering through microscopes, they carefully remove the “bad” cells to ensure the purity of the iPSCs they will provide to researchers at Cedars-Sinai and around the world.

While the cells get sorted, a special feeding formula is defrosting in a dozen bottles spread around a lab bench. The formula incudes sodium, glucose, vitamins and proteins. Using pipettes, employees squeeze the liquid into food wells inside little compartments that contain the iPSCs. Afterward, they return the cells to their incubators.

The lab’s 10 employees are on a rotating schedule that ensures the lab is staffed on weekends and holidays, not just weekdays. On Thanksgiving Day this year, biomedical technician Louis Pinedo expects to make a 100-mile round trip from his home in Oxnard, California, to spend several hours at work, filling nearly 600 feeding wells. On both Christmas and New Year’s Day, two employees are expected to staff the lab.

All this ceaseless effort helps make Cedars-Sinai one of the world’s top providers of iPSCs, renowned for consistency and quality. Among the lab’s many clients are major universities and the global Answer ALS project, which is using the cells in its search for a cure for this devastating disease.

That’s why the lab’s director, Dhruv Sareen, PhD, suggests that before you sit down to your Thanksgiving feast, why not lift a glass to these hard-working lab employees?

“One day the cells they tend could lead to treatments for diseases that have plagued humankind for centuries,” he says. “And that’s something to be truly thankful for.”

Machine learning used to pattern stem cells – a vital step in organ modeling

Gladstone researchers discovered a method to control the patterns stem cells form in a dish. The work was led by Senior Investigator Todd McDevitt (left) and his team, including (pictured) David Joy and Ashley Libby.

When someone thinks of machine learning, the first thing that comes to mind might be the technology used by Netflix or Hulu to suggest new shows based on their viewing history. But what if this technology could be applied towards advancing the field of regenerative medicine?

Thanks to a CIRM funded study, a team of scientists lead by Dr. Todd McDevitt at the Gladstone Institutes have found a way to to use machine learning to control the spacial organization of stem cells, a key process that plays a vital role in organ development. This new understanding of how stem cells organize themselves in 3D is an important step towards being able to create functional and/or personalized organs for research or organ transplants.

“We’ve shown how we can leverage the intrinsic ability of stem cells to organize,” said Dr. McDevitt in a news release from Gladstone Institutes. “This gives us a new way of engineering tissues, rather than a printing approach where you try to physically force cells into a specific configuration.”

In their normal environment, stem cells are able to form patterns as they mature and over time morph into the tissues seen in an adult organism. One type of stem cell, called an induced pluripotent stem cell (iPSC), can become nearly every cell type of the body. In fact, researchers have already found ways to direct iPSCs to become various cell types such as those in the heart or brain.

Unfortunately, attempting to replicate the pattern formation of stem cells as they mature has been challenging. Some have used 3D printing to lay out stem cells in a desired shape, but the cells often migrated away from their initial locations.

In the same news release mentioned above, Ashley Libby, a graduate student at Gladstone and co-first author of this study, said that,

“Despite the importance of organization for functioning tissues, we as scientists have had difficulty creating tissues in a dish with stem cells. Instead of an organized tissue, we often get a disorganized mix of different cell types.”

To solve this problem, the scientists used a computational model to learn how to influence stem cells into forming new arrangements, such as those that might be useful in generating personalized organs.

Previous studies conducted by Dr. McDevitt showed that blocking the expression of two genes, called ROCK1 and CDH1, affected the layout of iPS cells grown in a petri dish.

In this current study, the scientists used CRISPR/Cas9 gene editing (you can read about this technology in more detail here) to block expression of ROCK1 and CDH1 at any time by adding a drug to the iPSCs. This was done to see if they could predict stem cell arrangement based on the alterations made to ROCK1 and CDH1 at different drug doses and time periods.

The team carried out various experiments with different doses and timing. Then, the data was input into a machine-learning program designed to identify patterns, something that could take a human months to identify.

(Left) video showing simulated interactions between different stem cell populations. (Right) image of stem cells grown in conditions dictated by the machine-learning program generate a colony that forms a bull’s-eye pattern, as predicted.

The machine-learning program used the data to predict ways that ROCK1 and CDH1 affect iPSC organization. The scientists then began to see whether the program could compute how to make entirely new patterns, like a bull’s-eye or an island of cells. The team says the results were little short of astounding. Machine learning was able to accurately predict conditions that will cause stem cell colonies to form desired patterns.

The full study was published in the journal Cell Systems.

Rare Disease, Type 1 Diabetes, and Heart Function: Breakthroughs for Three CIRM-Funded Studies

This past week, there has been a lot of mention of CIRM funded studies that really highlight the importance of the work we support and the different disease areas we make an impact on. This includes important research related to rare disease, Type 1 Diabetes (T1D), and heart function. Below is a summary of the promising CIRM-funded studies released this past week for each one of these areas.

Rare Disease

Comparison of normal (left) and Pelizaeus-Merzbacher disease (PMD) brains (right) at age 2. 

Pelizaeus-Merzbacher disease (PMD) is a rare genetic condition affecting boys. It can be fatal before 10 years of age and symptoms of the disease include weakness and breathing difficulties. PMD is caused by a disruption in the formation of myelin, a type of insulation around nerve fibers that allows electrical signals in the brain to travel quickly. Without proper signaling, the brain has difficulty communicating with the rest of the body. Despite knowing what causes PMD, it has been difficult to understand why there is a disruption of myelin formation in the first place.

However, in a CIRM-funded study, Dr. David Rowitch, alongside a team of researchers at UCSF, Stanford, and the University of Cambridge, has been developing potential stem cell therapies to reverse or prevent myelin loss in PMD patients.

Two new studies, of which Dr. Rowitch is the primary author, published in Cell Stem Cell, and Stem Cell Reports, respectively report promising progress in using stem cells derived from patients to identify novel PMD drugs and in efforts to treat the disease by directly transplanting neural stem cells into patients’ brains. 

In a UCSF press release, Dr. Rowitch talks about the implications of his findings, stating that,

“Together these studies advance the field of stem cell medicine by showing how a drug therapy could benefit myelination and also that neural stem cell transplantation directly into the brains of boys with PMD is safe.”

Type 1 Diabetes

Viacyte, a company that is developing a treatment for Type 1 Diabetes (T1D), announced in a press release that the company presented preliminary data from a CIRM-funded clinical trial that shows promising results. T1D is an autoimmune disease in which the body’s own immune system destroys the cells in the pancreas that make insulin, a hormone that enables our bodies to break down sugar in the blood. CIRM has been funding ViaCyte from it’s very earliest days, investing more than $72 million into the company.

The study uses pancreatic precursor cells, which are derived from stem cells, and implants them into patients in an encapsulation device. The preliminary data showed that the implanted cells, when effectively engrafted, are capable of producing circulating C-peptide, a biomarker for insulin, in patients with T1D. Optimization of the procedure needs to be explored further.

“This is encouraging news,” said Dr. Maria Millan, President and CEO of CIRM. “We are very aware of the major biologic and technical challenges of an implantable cell therapy for Type 1 Diabetes, so this early biologic signal in patients is an important step for the Viacyte program.”

Heart Function

Although various genome studies have uncovered over 500 genetic variants linked to heart function, such as irregular heart rhythms and heart rate, it has been unclear exactly how they influence heart function.

In a CIRM-funded study, Dr. Kelly Frazer and her team at UCSD studied this link further by deriving heart cells from induced pluripotent stem cells. These stem cells were in turn derived from skin samples of seven family members. After conducting extensive genome-wide analysis, the team discovered that many of these genetic variations influence heart function because they affect the binding of a protein called NKX2-5.

In a press release by UCSD, Dr. Frazer elaborated on the important role this protein plays by stating that,

“NKX2-5 binds to many different places in the genome near heart genes, so it makes sense that variation in the factor itself or the DNA to which it binds would affect that function. As a result, we are finding that multiple heart-related traits can share a common mechanism — in this case, differential binding of NKX2-5 due to DNA variants.”

The full results of this study were published in Nature Genetics.

CIRM funded study identifies potential drug target for deadly heart condition

Joseph Wu is co-senior author of a study that demonstrates how patient-derived heart cells can help scientists better study the heart and screen potential therapies. Photo courtesy of Steve Fisch

Heart disease continues to be the number one cause of death in the United States. An estimated 375,000 people have a genetic form of heart disease known as familial dilated cardiomyopathy. This occurs when the heart muscle becomes weakened in one chamber in the heart, causing the open area of the chamber to become enlarged or dilated. As a result of this, the heart can no longer beat regularly, causing shortness of breath, chest pain and, in severe cases, sudden and deadly cardiac arrest.

A diagram of a normal heart compared to one with the dilated cardiomyopathy

A CIRM funded study by a team of researchers at Stanford University looked further into this form of genetic heart disease by taking a patient’s skin cells and converting them into stem cells known as induced pluripotent stem cells (iPSCs), which can become any type of cell in the body. These iPSCs were then converted into heart muscle cells that pulse just as they do in the body. These newly made heart muscle cells beat irregularly, similar to what is observed in the genetic heart condition.

Upon further analysis, the researchers linked a receptor called PGDF to cause various genes to be more highly activated in the mutated heart cells compared to normal ones. Two drugs, crenolanib and sunitinib, interfere with the PGDF receptor. After treating the abnormal heart cells, they began beating more regularly, and their gene-activation patterns more closely matched those of cells from healthy donors.

These two drugs are already FDA-approved for treating various cancers, but previous work shows that the drugs may damage the heart at high doses. The next step would be determining the right dose of the drug. The current study is part of a broader effort by the researchers to use these patient-derived cells-in-a-dish to screen for and discover new drugs.

Dr. Joseph Wu, co-senior author of this study, and his team have generated heart muscle cells from over 1,000 patients, including those of Dr. Wu, his son, and his daughter. In addition to using skin cells, the same technique to create heart cells from patients can also be done with 10 milliliters of blood — roughly two teaspoons.

In a news release, Dr. Wu is quoted as saying,

“With 10 milliliters of blood, we can make clinically usable amounts of your beating heart cells in a dish…Our postdocs have taken my blood and differentiated my pluripotent stem cells into my brain cells, heart cells and liver cells. I’m asking them to test some of the medications that I might need to take in the future.”

The full results of this study were published in Nature.

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.