UCSD researchers use stem cell model to better understand pregnancy complication

A team of UC San Diego researchers recently published novel preeclampsia models to aid in understanding this pregnancy complication that occurs in one of 25 U.S. pregnancies. Researchers include (left to right): Ojeni Touma, Mariko Horii, Robert Morey and Tony Bui. Credit: UC San Diego

Pregnant women often tread uncertain waters in regards to their health and well-being as well as that of their babies. Many conditions can arise and one of these is preeclampsia, a type of pregnancy complication that occurs in approximately one in 25 pregnancies in the United States according to the Center for Disease Control (CDC). It occurs when expecting mothers develop high blood pressure, typically after 20 weeks of pregnancy, and that in turn reduces the blood supply to the baby. This can lead to serious, even fatal, complications for both the mother and baby.

A CIRM supported study using induced pluripotent stem cells (iPSCs), a kind of stem cell that can turn into virtually any cell type, was able to create a “disease in a dish” model in order to better understand preeclampsia.

Credit: UC San Diego

For this study, Mariko Horii, M.D., and her team of researchers at the UC San Diego School of Medicine obtained cells from the placenta of babies born under preeclampsia conditions. These cells were then “reprogrammed” into a stem cell-like state, otherwise known as iPSCs. The iPSCs were then turned into cells resembling placental cells in early pregnancy. This enabled the team to create the preeclampsia “disease in the dish” model. Using this model, they were then able to study the processes that cause, result from, or are otherwise associated with preeclampsia.

The findings revealed that cellular defects observed are related to an abnormal response in the environment in the womb. Specifically, they found that preeclampsia was associated with a low-oxygen environment in the uterus. The researchers used a computer modeling system at UC San Diego known as Comet to detail the differences between normal and preeclampsia placental tissue.

Horii and her team hope that these findings not only shed more light on the environment in the womb observed in preeclampsia, but also provided insight for future development of diagnostic tools and identification of potential medications. Furthermore, they hope that their iPSC disease model can be used to study other placenta-associated pregnancy disorders such as fetal growth restriction, miscarriage, and preterm birth.

The team’s next steps are to develop a 3D model to better study the relationship between environment and development of placental disease.

In a news release from UC San Diego, Horri elaborates more on these future goals.

“Currently, model systems are in two-dimensional cultures with single-cell types, which are hard to study as the placenta consists of maternal and fetal cells with multiple cell types, such as placental cells (fetal origin), maternal immune cells and maternal endometrial cells. Combining these cell types together into a three-dimensional structure will lead to a better understanding of the more complex interactions and cell-to-cell signaling, which can then be applied to the disease setting to further understand pathophysiology.”

The full study was published in Scientific Reports.

Stem cell treatment improves motor function in monkeys modeling Parkinson’s Disease

Neurodegenerative diseases impact millions of people worldwide with the risk of being affected by one of these diseases increasing as you get older. For many of these diseases, there are very few treatments available to patients. As life expectancy increases and the population continues to age, it is crucial to try and find treatments that can potentially slow the progression of these diseases or cure them entirely. This is one of the reasons why CIRM has committed directing around $1.5 billion in funding over the next few years to research related to neurological disorders.

One of the most common neurodegenerative diseases is Parkinson’s Disease (PD), a movement disorder that affects one million people in the U.S alone and leads to shaking, stiffness, insomnia, fatigue, and problems with walking, balance, and coordination.  It is caused by the breakdown and death of dopaminergic neurons, special nerve cells in the brain responsible for the production of dopamine, a chemical messenger that is crucial for normal brain activity.

A recent study published in Nature Medicine has shown improved motor function and growth of neurons over a two year period in monkeys modeling PD. The study was conducted by Su-Chun Zhang, M.D., Ph.D. and his team at the University of Wisconsin using induced pluripotent stem cells (iPSCs), a kind of stem cell that can become virtually any type of cell that can be made from skin cells. The hope is that these results can pave the way for starting human clinical trials.

In order to replicate PD in humans, the team injected 10 adult monkeys with a neurotoxin that produces PD like symptoms. As a result of this, all 10 monkeys developed slow movements, imbalances, tremors, and impaired coordination in the hand on the opposite side of the injection. Additionally, scans revealed that on the injected side, monkeys lost most brain activity involving dopamine in two key brain areas. The team then waited three years after injecting the neurotoxin before administering the therapy, during which time the monkeys’ symptoms persisted.

To generate iPSC lines, the team obtained skin cells from five of the monkeys. The iPSCs were then turned into dopamine neural progenitor cells, which have the ability to create dopamine. These newly created cells were then administered into the brains of the five monkeys, with each monkey receiving a treatment derived from their own skin cells. A sixth iPSC line from a donor monkey was used for the remaining five monkeys to see how the treatment would work if it was not derived from their own skin cells.

The results showed that the monkeys that received the treatment derived from their own skin cells recovered. These animals moved more, moved faster, and were nimbler than before the treatment. They gained the ability to grasp treats, use all four limbs for walking, and climb their cages with ease and increased agility. However, the monkeys that received iPSCs derived from a donor did not recover. Their symptoms remained unchanged or worsened compared to before the treatment.

In a news article, Zhang emphasizes how he and his team are proceeding with a treatment derived from one’s own cells (autologous) vs. one from a donor (allogeneic).

“I initially wanted to do allogeneic transplants in patients because the autologous approach is too expensive. However, after seeing [our] data, I changed my mind. I want to go with the autologous first… because I feel the chance of success is really, really high.”

CIRM is currently funding a human clinical trial ($5.5 million) that is using a gene therapy approach for PD.

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.”

Friday Round Up

Here’s a look at a couple of stories that caught our eye this week:

Jasper Therapeutics has had a busy couple of weeks. Recently they announced data from their Phase 1 clinical trial treating people with Myelodysplastic syndromes (MDS). This is a group of disorders in which immature blood-forming cells in the bone marrow become abnormal and leads to low numbers of normal blood cells, especially red blood cells. We blogged about that here.

The data showed that six patients were given JSP191 – in combination with low-dose radiation five of the six had no detectable levels of disease and the sixth patient had reduced levels.

This was a big deal for us because CIRM funded the early stage research and even a clinical trial  that led to the development of JSP191.

Now Jasper has announced it is partnering with the National Institute of Allergy and Infectious Disease in a Phase 1/2 clinical trial using JSP191, as part of a treatment for chronic granulomatous disease (CGD). Congratulations to Jasper. And congratulations to us for helping them get there.

Oh, and just to toot our horn a little bit more – it is Friday after all – we have funded other approaches to CGD including one that resulted in curing Brenden Whittaker.

OK, enough about us.

To say that this last year has been a stressful one would be something of an understatement. But it’s not just people who get stressed. Stem cells do too. And, like people, when stem cells get stressed they don’t always behave in the way you would like them to. When some people get stressed they find a cocktail can help take the edge of it. Apparently that works for stem cells as well!

Now we are not talking about slipping a Manhattan or Mai Tai into a petri dish filled with stem cells. We are talking about a very different kind of cocktail.

Researchers at the National Institutes of Health have developed what they describe as a “four-part small molecule cocktail” that can help protect a specific kind of stem cell from stress. The cell is an induced pluripotent stem cell (iPSC), which has the ability to turn into any other kind of cell in the body. iPSC’s have great potential for treating a variety of different diseases and conditions, but they’re also sensitive and without the right conditions and environment they can get stressed and that in turn can damage their DNA and lead to them dying.

In a news release Dr. Ilyas Singeç, the lead researcher, says this NIH “cocktail” could help prevent that: “The small-molecule cocktail is safeguarding cells and making stem cell use more predictable and efficient. In preventing cellular stress and DNA damage that typically occur, we’re avoiding cell death and improving the quality of surviving cells. The cocktail will become a broadly used staple of the stem cell field and boost stem cell applications in both research and the clinic.”  

The team hope this could enhance the potential therapeutic uses of iPSCs in finding treatments for diseases such as diabetes, Parkinson’s and spinal cord injury.

The study is published in the journal Nature Methods.

CIRM funded study uses drug development in a dish for treatment of heart arrhythmias

Image Credit: Center for Disease Control and Prevention (CDC)

Cardiac (heart) arrhythmias occur when electrical impulses that coordinate your heartbeats don’t work properly, causing your heart to beat too fast, too slow, or in an irregular manner. In the U.S. alone, almost one million individuals are hospitalized every year for heart arrhythmias. Close to 300,000 individuals die of sudden arrhythmic death syndrome every year, which occurs when there is a sudden loss of blood flow resulting from the failure of the heart to pump effectively. Unfortunately, drugs to treat arrhythmias have liabilities and several drugs have been pulled from the market due to serious side effects. Mexiletine is one potential drug for heart arrhythmias that has liabilities and potential side effects.

That is why a CIRM funded study ($6.3 million) conducted by John Cashman, Ph.D. at the Human BioMolecular Research Institute in San Diego looked at re-engineering mexiletine in a way that the drug could still produce a desired result and not be as toxic.

The study used induced pluripotent stem cells (iPSCs), a type of stem cell “reprogrammed” from the skin or blood of patients that can be used to make virtually any kind of cell. iPSCs obtained for the study were from a healthy patient and from one with a type of heart arrhythmia. The healthy and arrhythmia iPSCs were then converted into cardiomyocytes, a type of cell that makes up the heart muscle.

By using their newly created healthy cardiomyocytes and those with the arrhythmia defect, Cashman and his team were able to carry out drug development in a dish. This enabled them to attempt to lessen drug toxicity while still potentially treating heart arrhythmias. The team was able to modify mexiletine such that is was less toxic and found that it could potentially decrease a patient’s risk of developing ventricular tachycardia (a fast, abnormal heart rate) and ventricular fibrillation (an abnormal heart rhythm), both of which are types of heart arrhythmias.

“The new compounds may lead to treatment applications in a whole host of cardiovascular conditions that may prove efficacious in clinical trials,” said Cashman in a press release. “As antiarrhythmic drug candidate drug development progresses, we expect the new analogs to be less toxic than current therapeutics for arrhythmia in congenital heart disease, and patients will benefit from improved safety, less side effects and possibly with significant cost-savings.”

The team hopes that their study can pave the way for future research in which cells in a dish can be used to lessen the toxicity of a potential drug candidate while still producing a desired result for different diseases and conditions.

The full study was published in ACS Publications.

CIRM funded researchers discover link between Alzheimer’s gene and COVID-19

Dr. Yanhong Shi (left) and Dr. Vaithilingaraja Arumugaswami (right)

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we focus on groundbreaking CIRM funded research related to COVID-19 that was recently published.

It’s been almost a year since the world started hearing about SARS-CoV-2, the virus that causes COVID-19.  In our minds, the pandemic has felt like an eternity, but scientists are still discovering new things about how the virus works and if genetics might play a role in the severity of the virus.  One population study found that people who have ApoE4, a gene type that has been found to increase the risk of developing Alzheimer’s, had higher rates of severe COVID-19 and hospitalizations.

It is this interesting observation that led to important findings of a study funded by two CIRM awards ($7.4M grant and $250K grant) and conducted by Dr. Yanhong Shi at City of Hope and co-led by Dr. Vaithilingaraja Arumugaswami, a member of the UCLA Broad Stem Cell Research Center.  The team found that the same gene that increases the risk for Alzheimer’s disease can increase the susceptibility and severity of COVID-19.

At the beginning of the study, the team was interested in the connection between SARS-CoV-2 and its effect on the brain.  Due to the fact that patients typically lose their sense of taste and smell, the team theorized that there was an underlying neurological effect of the virus.  

The team first created neurons and astrocytes.  Neurons are cells that function as the basic working unit of the brain and astrocytes provide support to them.  The neurons and astrocytes were generated from induced pluripotent stem cells (iPSCs), which are a kind of stem cell that can become virtually any type of cell and can be created by “reprogramming” the skin cells of patients.  The newly created neurons and astrocytes were then infected with SARS-CoV-2 and it was found that they were susceptible to infection.

Next, the team used iPSCs to create brain organoids, which are 3D models that mimic certain features of the human brain.  They were able to create two different organoid models: one that contained astrocytes and one without them.  They infected both brain organoid types with the virus and discovered that those with astrocytes boosted SARS-CoV-2 infection in the brain model. 

The team then decided to further study the effects of ApoE4 on susceptibility to SARS-CoV-2.  They did this by generating neurons from iPSCs “reprogrammed” from the cells of an Alzheimer’s patient.  Because the iPSCs were derived from an Alzheimer’s patient, they contained ApoE4.  Using gene editing, the team modified some of the ApoE4 iPSCs created so that they contained ApoE3, which is a gene type considered neutral.  The ApoE3 and ApoE4 iPSCs were then used to generate neurons and astrocytes.

The results were astounding.  The ApoE4 neurons and astrocytes both showed a higher susceptibility to SARS-CoV-2 infection in comparison to the ApoE3 neurons and astrocytes.  Moreover, while the virus caused damage to both ApoE3 and ApoE4 neurons, it appeared to have a slightly more severe effect on ApoE4 neurons and a much more severe effect on ApoE4 astrocytes compared to ApoE3 neurons and astrocytes. 

“Our study provides a causal link between the Alzheimer’s disease risk factor ApoE4 and COVID-19 and explains why some (e.g. ApoE4 carriers) but not all COVID-19 patients exhibit neurological manifestations” says Dr. Shi. “Understanding how risk factors for neurodegenerative diseases impact COVID-19 susceptibility and severity will help us to better cope with COVID-19 and its potential long-term effects in different patient populations.”

In the last part of the study, the researchers tested to see if the antiviral drug remdesivir inhibits virus infection in neurons and astrocytes.  They discovered that the drug was able to successfully reduce the viral level in astrocytes and prevent cell death.  For neurons, it was able to rescue them from steadily losing their function and even dying. 

The team says that the next steps to build on their findings is to continue studying the effects of the virus and better understand the role of ApoE4 in the brains of people who have COVID-19.  Many people that developed COVID-19 have recovered, but long-term neurological effects such as severe headaches are still being seen months after. 

“COVID-19 is a complex disease, and we are beginning to understand the risk factors involved in the manifestation of the severe form of the disease” says Dr. Arumugaswami.  “Our cell-based study provides possible explanation to why individuals with Alzheimer’s’ disease are at increased risk of developing COVID-19.”

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

Stem cell research reveals path to schizophrenia

3d illustration of brain nerve cells – Photo courtesy Science Photo

If you don’t know what’s causing a problem it’s hard to come up with a good way to fix it. Mental health is the perfect example. With a physical illness you can see what the problem is, through blood tests or x-rays, and develop a plan to tackle it. But with the brain, that’s a lot harder. You can’t autopsy a brain while someone is alive, they tend to object, so you often only see the results of a neurological illness when they’re dead.

And, says Consuelo Walss-Bass, PhD, a researcher at the University of Texas Health Science Center at Houston (UTHealth), with mental illness it’s even more complicated.

“Mental health research has lagged behind because we don’t know what is happening biologically. We are diagnosing people based on what they are telling us. Even postmortem, the brain tissue in mental health disorders looks perfectly fine. In Alzheimer’s disease, you can see a difference compared to controls. But not in psychiatric disorders.”

So Wals-Bass and her team came up with a way to see what was going on inside the brain of someone with schizophrenia, in real time, to try and understand what puts someone at increased risk of the disorder.

In the study, published in the journal Neuropsychopharmacology, the researchers took blood samples from a family with a high incidence of schizophrenia. Then, using the iPSC method, they turned those cells into brain neurons and compared them to the neurons of individuals with no family history of schizophrenia. In effect, they did a virtual brain biopsy.

By doing this they were able to identify five genes that had previously been linked to a potential higher risk of schizophrenia and then narrow that down further, highlighting one gene called SGK1 which blocked an important signalling pathway in the brain.

In a news release, Walss-Bass says this findings could have important implications in treating patients.

“There is a new antipsychotic that just received approval from the Food and Drug Administration that directly targets the pathway we identified as dysregulated in neurons from the patients, and several other antipsychotics also target this pathway. This could help pinpoint who may respond better to treatments.”

Finding the right treatment for individual patients is essential in helping them keep their condition under control. A study in the medical journal Lancet estimated that six months after first being prescribed common antipsychotic medication, as many as 50% of patients are either taking the drugs haphazardly or not at all. That’s because they often come with unpleasant side effects such as weight gain, drowsiness and a kind of restless anxiety.

By identifying people who have specific gene pathways linked to schizophrenia could help us better tailor medications to those who will benefit most by them.

Persistence pays off in search for clue to heart defects

A team of scientists led by Benoit Bruneau (left), including Irfan Kathiriya (center) and Kavitha Rao (right), make inroads into understanding what genes are improperly deployed in some cases of congenital heart disease.  Photo courtesy Gladstone Institute

For more than 20 years Dr. Benoit Bruneau has been trying to identify the causes of congenital heart disease, the most common form of birth defect in the U.S. It turns out that it’s not one cause, but many.

Congenital heart disease covers a broad range of defects, some relatively minor and others life-threatening and even fatal. It’s been known that a mutation in a gene called TBX5 is responsible for some of these defects, so, in a CIRM-funded study ($1.56 million), Bruneau zeroed in on this mutation to see if it could help provide some answers.

In the past Bruneau, the director of the Gladstone Institute of Cardiovascular Disease, had worked with a mouse model of TBX5, but this time he used human induced pluripotent stem cells (iPSCs). These are cells that can be manipulated in the lab to become any kind of cell in the human body. In a news release Bruneau says this was an important step forward.

“This is really the first time we’ve been able to study this genetic mutation in a human context. The mouse heart is a good proxy for the human heart, but it’s not exactly the same, so it’s important to be able to carry out these experiments in human cells.”

The team took some iPSCs, changed them into heart cells, and used a gene editing tool called CRISPR-Cas9 to create the kinds of mutations in TBX5 that are seen in people with congenital heart disease. What they found was some genes were affected a lot, some not so much. Which is what you might expect in a condition that causes so many different forms of problems.

“It makes sense that some are more affected than others, but this is the first experimental data in human cells to show that diversity,” says Bruneau.

But they didn’t stop there. Oh no. Then they did a deep dive analysis to understand how the different ways that different cells were impacted related to each other. They found some cells were directly affected by the TBX5 mutation but others were indirectly affected.

The study doesn’t point to a simple way of treating congenital heart disease but Bruneau says it does give us a much better understanding of what’s going wrong, and perhaps will give us better ideas on how to stop that.

“Our new data reveal that the genes are really all part of one network—complex but singular—which needs to stay balanced during heart development. That means if we can figure out a balancing factor that keeps this network functioning, we might be able to help prevent congenital heart defects.”

The study is published in the journal Developmental Cell.

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

Biomedical specialist Mamadou Dialio at work in the Cedars-Sinai Biomanufacturing Center. Photo by Cedars-Sinai.

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

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

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

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

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

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

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

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

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

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

Precision guided therapy from a patient’s own cells

Dr. Wesley McKeithan, Stanford

Imagine having a tool you could use to quickly test lots of different drugs against a disease to see which one works best. That’s been a goal of stem cell researchers for many years but turning that idea into a reality hasn’t been easy. That may be about to change.

A team of CIRM-funded researchers at the Stanford Cardiovascular Institute and the Human BioMolecular Research Institute in San Diego found a way to use stem cells from patients with a life-threatening heart disease, to refine an existing therapy to make it more effective, with fewer side effects.

The disease in question is called long QT syndrome (LQTS). This is a heart rhythm condition that can cause fast, chaotic heartbeats. Some people with the condition have seizures. In some severe cases, particularly in younger people, LQTS can cause sudden death.

There are a number of medications that can help keep LQTS under control. One of these is mexiletine. It’s effective at stabilizing the heart’s rhythm, but it also comes with some side effects such as stomach pain, chest discomfort, drowsiness, headache, and nausea.

The team wanted to find a way to test different forms of that medication to see if they could find one that worked better and was safer to take. So they used induced pluripotent stem cells (iPSCs) from patients with LQTS to do just that.

iPSCs are cells that are made from human tissue – usually skin – that can then be turned into any other cell in the body. In this case, they took tissue from people with LQTS and then turned them into heart cells called cardiomyocytes, the kind affected by the disease. The beauty of this technique is that even though these cells came from another source, they now look and act like cardiomyocytes affected by LQTS.

Dr. Mark Mercola, Stanford

In a news release Stanford’s Dr. Mark Mercola, the senior author of the study, said using these kinds of cells gave them a powerful tool.

“Drugs for heart disease are typically developed using overly simplified models, like tumor cells engineered in a specific way to mimic a biochemical event. Consequently, drugs like this one, mexiletine, have undesirable properties of concern in treating patients. Here, we used cells from a patient to generate that person’s heart muscle cells in a dish so we could visualize both the good and bad effects of the drug.”

The researchers then used these man-made cardiomyocytes to test various drugs that were very similar in structure to mexiletine. They were looking for ones that could help stabilize the heart arrhythmia but didn’t produce the unpleasant side effects. And they found some promising candidates.

Study first author, Dr. Wesley McKeithan, says the bigger impact of the study is that they were able to show how this kind of cell from patients with a particular disease can be used to “guide drug development and identify better drug improvement and optimization in a large-scale manner.”

 “Our approach shows the feasibility of introducing human disease models early in the drug development pipeline and opens the door for precision drug design to improve therapies for patients.”

The study is published in the journal Cell Stem Cell.