Of Mice and Men, and Women Too; Stem cell stories you might have missed

Mice brains can teach us a lot

Last week’s news headlines were dominated by one big story, the use of a stem cell transplant to effectively cure a person of HIV. But there were other stories that, while not quite as striking, did also highlight how the field is advancing.

A new way to boost brain cells (in mice!)

It’s hard to fix something if you don’t really know what’s wrong in the first place. It would be like trying to determine why a car is not working just by looking at the hood and not looking inside at the engine. The human brain is far more complex than a car so trying to determine what’s going wrong is infinitely more challenging. But a new study could help give us a new option.

Researchers in Luxembourg and Germany have developed a new computer model for what’s happening inside the brain, identifying what cells are not operating properly, and fixing them.

Antonio del Sol, one of the lead authors of the study – published in the journal Cell – says their new model allows them to identify which stem cells are active and ready to divide, or dormant. 

“Our results constitute an important step towards the implementation of stem cell-based therapies, for instance for neurodegenerative diseases. We were able to show that, with computational models, it is possible to identify the essential features that are characteristic of a specific state of stem cells.”

The work, done in mice, identified a protein that helped keep brain stem cells inactive in older animals. By blocking this protein they were able to help “wake up” those stem cells so they could divide and proliferate and help regenerate the aging brain.

And if it works in mice it must work in people right? Well, that’s what they hope to see next.

Deeper understanding of fetal development

According to the Mayo Clinic between 10 and 20 percent of known pregnancies end in miscarriage (though they admit the real number may be even higher) and our lack of understanding of fetal development makes it hard to understand why. A new study reveals a previously unknown step in this development that could help provide some answers and, hopefully, lead to ways to prevent miscarriages.

Researchers at the Karolinska Institute in Sweden used genetic sequencing to follow the development stages of mice embryos. By sorting those different sequences into a kind of blueprint for what’s happening at every stage of development they were able to identify a previously unknown phase. It’s the time between when the embryo attaches to the uterus and when it begins to turn these embryonic stem cells into identifiable parts of the body.

Qiaolin Deng, Karolinska Institute

Lead researcher Qiaolin Deng says this finding provides vital new evidence.

“Being able to follow the differentiation process of every cell is the Holy Grail of developmental biology. Knowledge of the events and factors that govern the development of the early embryo is indispensable for understanding miscarriages and congenital disease. Around three in every 100 babies are born with fetal malformation caused by faulty cellular differentiation.”

The study is published in the journal Cell Reports.

Could a new drug discovery reduce damage from a heart attack?

Every 40 seconds someone in the US has a heart attack. For many it is fatal but even for those who survive it can lead to long-term damage to the heart that ultimately leads to heart failure. Now British researchers think they may have found a way to reduce that likelihood.

Using stem cells to create human heart muscle tissue in the lab, they identified a protein that is activated after a heart attack or when exposed to stress chemicals. They then identified a drug that can block that protein and, when tested in mice that had experienced a heart attack, they found it could reduce damage to the heart muscle by around 60 percent.

Prof Michael Schneider, the lead researcher on the study, published in Cell Stem Cell, said this could be a game changer.

“There are no existing therapies that directly address the problem of muscle cell death and this would be a revolution in the treatment of heart attacks. One reason why many heart drugs have failed in clinical trials may be that they have not been tested in human cells before the clinic. Using both human cells and animals allows us to be more confident about the molecules we take forward.”

A new and improved method for making healthy heart tissue is here

Scientists from the Gladstone Institutes have done it again. They’ve made a better and faster way of generating healthy heart tissue in mice with damaged hearts. With further advancements, their findings could potentially be translated into a new way of treating heart failure in patients.

Previously, the Gladstone team discovered that they could transform scar tissue in the damaged hearts of mice into healthy, beating heart muscle cells by a process called direct reprogramming. The team found that turning on three transcription factors, Gata4, Mef2c and Tbx5 (collectively called GMT), in the damaged hearts of mice activated heart genes that turned scar tissue cells, also known as cardiac fibroblasts, into beating heart cells or cardiomyocytes.

Their GMT direct cardiac reprogramming technology was only able to turn 10 percent of cardiac fibroblasts into cardiomyocytes in mice over the period of six to eight week. In their new CIRM-funded study published in Circulation, they improved upon their original reprogramming method by identifying two chemicals that improved the efficiency of making new heart cells. Not only were they able to create eight times the number of beating cardiomyocytes from mouse cardiac fibroblasts, but they were also able to speed up the reprogramming process to a period of just one week.

To find these chemicals, they screened a library of 5,500 small molecules. The chemicals that looked most promising for cardiac reprogramming were inhibitors of the TGF-β and WNT signaling pathways. The importance of these chemicals was explained in a Gladstone news release:

“The first chemical inhibits a growth factor that helps cells grow and divide and is important for repairing tissue after injury. The second chemical inhibits an important pathway that regulates heart development. By combining the two chemicals with GMT, the researchers successfully regenerated heart muscle and greatly improved heart function in mice that had suffered a heart attack.”

Senior author on the study, Deepak Srivastava, further explained:

“While our original process for direct cardiac reprogramming with GMT has been promising, it could be more efficient. With our screen, we discovered that chemically inhibiting two biological pathways active in embryonic formation improves the speed, quantity, and quality of the heart cells produced from our original process.”

Encouraged by their studies in mice, the scientists also tested their new and improved direct reprogramming method on human cells. Previously they found that while the same GMT transcription factors could reprogram human cardiac fibroblasts into cardiomyocytes, a combination of seven factors was required to make quality cardiomyocytes comparable to those seen in mice. But with the addition of the two inhibitors, they were able to reduce the number of reprogramming factors from seven to four, which included the GMT factors and one additional factor called Myocardin. These four factors plus the two chemical inhibitors were capable of reprograming human cardiac fibroblasts into beating heart cells.

With heart failure affecting more than 20 million people globally, the need for new therapies that can regenerate the heart is pressing. The Gladstone team is hoping to advance their research to a point where it could be tested in human patients with heart failure. First author on the study, Tamer Mohamed, concluded:

“Heart failure afflicts many people worldwide, and we still do not have an effective treatment for patients suffering from this disease. With our enhanced method of direct cardiac reprogramming, we hope to combine gene therapy with drugs to create better treatments for patients suffering from this devastating disease.”

Tamer Mohamed and Deepak Srivastava, Gladstone Institutes

Tamer Mohamed and Deepak Srivastava. Photo courtesy of Chris Goodfellow, Gladstone Institutes


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Using skin cells to repair damaged hearts

heart-muscle

Heart muscle  cells derived from skin cells

When someone has a heart attack, getting treatment quickly can mean the difference between life and death. Every minute delay in getting help means more heart cells die, and that can have profound consequences. One study found that heart attack patients who underwent surgery to re-open blocked arteries within 60 minutes of arriving in the emergency room had a six times greater survival rate than people who had to wait more than 90 minutes for the same treatment.

Clearly a quick intervention can be life-saving, which means an approach that uses a patient’s own stem cells to treat a heart attack won’t work. It simply takes too long to harvest the healthy heart cells, grow them in the lab, and re-inject them into the patient. By then the damage is done.

Now a new study shows that an off-the-shelf approach, using donor stem cells, might be the most effective way to go. Scientists at Shinshu University in Japan, used heart muscle stem cells from one monkey, to repair the damaged hearts of five other monkeys.

In the study, published in the journal Nature, the researchers took skin cells from a macaque monkey, turned those cells into induced pluripotent stem cells (iPSCs), and then turned those cells into cardiomyocytes or heart muscle cells. They then transplanted those cardiomyocytes into five other monkeys who had experienced an induced heart attack.

After 3 months the transplanted monkeys showed no signs of rejection and their hearts showed improved ability to contract, meaning they were pumping blood around the body more powerfully and efficiently than before they got the cardiomyocytes.

It’s an encouraging sign but it comes with a few caveats. One is that the monkeys used were all chosen to be as close a genetic match to the donor monkey as possible. This reduced the risk that the animals would reject the transplanted cells. But when it comes to treating people, it may not be feasible to have a wide selection of heart stem cell therapies on hand at every emergency room to make sure they are a good genetic match to the patient.

The second caveat is that all the transplanted monkeys experienced an increase in arrhythmias or irregular heartbeats. However, Yuji Shiba, one of the researchers, told the website ResearchGate that he didn’t think this was a serious issue:

“Ventricular arrhythmia was induced by the transplantation, typically within the first four weeks. However, this post-transplant arrhythmia seems to be transient and non-lethal. All five recipients of [the stem cells] survived without any abnormal behaviour for 12 weeks, even during the arrhythmia. So I think we can manage this side effect in clinic.”

Even with the caveats, this study demonstrates the potential for a donor-based stem cell therapy to treat heart attacks. This supports an approach already being tested by Capricor in a CIRM-funded clinical trial. In this trial the company is using donor cells, derived from heart stem cells, to treat patients who developed heart failure after a heart attack. In early studies the cells appear to reduce scar tissue on the heart, promote blood vessel growth and improve heart function.

The study from Japan shows the possibilities of using a ready-made stem cell approach to helping repair damage caused by a heart attacks. We’re hoping Capricor will take it from a possibility, and turn it into a reality.

If you would like to read some recent blog posts about Capricor go here and here.

Ready, Set, Go: CIRM funded clinical trial for heart disease finishes patient enrollment

Heart disease is the leading cause of death in the United States with over 600,000 deaths occurring per year. Patients with heart disease or heart failure are given treatments that attempt to prevent their condition from getting worse or improve some of their symptoms. However, no treatment exists that can completely restore their heart function except for having a heart transplant – a risky procedure that has significant obstacles associated with it including transplant rejection and limited donor availability.

Regenerative medicine research for heart disease is an up-and-coming field. Scientist and companies are testing stem cell-based therapies to treat patients with heart disease in hopes of improving or restoring heart function.

capricor

CIRM is funding a company called Capricor Therapeutics located in Los Angeles, California, that’s testing a stem cell-based therapy in a Phase II clinical trial for cardiac dysfunction called ALLSTAR (ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration).  The treatment is called  CAP-1002, which is an infusion of allogeneic cardiosphere-derived cells (CDCs). Capricor has shown that CDCs can regenerate tissue in the injured human heart in a previous Phase I clinical trial called CADUCEUS, which treated patients one to three months after they had a heart attack.

This week, Capricor reported that it has passed another milestone in the ALLSTAR trial and finished patient enrollment. Compared to the CADUCEUS trial, the patient population in ALLSTAR was expanded to include individuals that had a heart attack in the past 12 months. The purpose of this expanded patient population is to determine whether CAP-1002 is beneficial to patients with older heart injuries. A total of 142 patients were enrolled in the trial and 134 of those patients received either a single injection of CAP-1002 or a placebo treatment into their coronary artery associated with the heart injury.

In a news release, Capricor President and CEO Linda Marban explained the logic behind the CADUCEUS and ALLSTAR trials for cardiac dysfunction:

Linda Marban, CEO of Capricor Therapeutics

Linda Marban, CEO of Capricor Therapeutics

“As we and others have shown, CAP-1002 possesses the ability to promote therapeutic regeneration in the injured heart, a powerful concept for the treatment of heart disease. In the CADUCEUS clinical trial, CDCs decreased scar size and increased viable tissue in the hearts of patients who had suffered a large heart attack. In ALLSTAR, not only are we studying a population similar to the one that delivered such astounding results in CADUCEUS (30 – 90 days post-MI), but we have also included patients that were 91 – 365 days post-MI to see if we could extend the indication window. We have also moved to an allogeneic platform from autologous cells.”

ALLSTAR patients will be monitored carefully over the next year to make sure the CAP-1002 treatment is safe. After a year, Capricor will assess the potential regenerative capacity of CAP-1002 by measuring the size of the heart injury and looking for a reduction in scar tissue using magnetic resonance imaging (MRI).

“With the last patient in ALLSTAR having been dosed on September 30th, we expect to report top-line 12-month primary efficacy outcome results in the fourth quarter of 2017,” said Marban. “We are very much looking forward to seeing the results of the ALLSTAR trial because they may show, for the first time in a Phase II clinical trial, that cells can reduce scar and potentially improve outcomes.”

CIRM is also funding another clinical trial by Capricor that’s evaluating CAP-1002 in young boys with cardiomyopathy – diseases that affect heart muscle – resulting from Duchenne muscular dystrophy. The Phase I/II trial called HOPE recently completed its patient enrollment and you can read more about it here on the Stem Cellar.


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Out of the mouths, or in this case hearts, of babes comes a hopeful therapy for heart attack patients

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Lessons learned from babies with heart failure could now help adults

Inspiration can sometimes come from the most unexpected of places. For English researcher Stephen Westaby it came from seeing babies who had heart attacks bounce back and recover. It led Westaby to a new line of research that could offer hope to people who have had a heart attack.

Westaby, a researcher at the John Radcliffe hospital in Oxford, England, found that implanting a novel kind of stem cell in the hearts of people undergoing surgery following a heart attack had a surprisingly significant impact on their recovery.

Westaby got his inspiration from studies showing babies who had a heart attack and experienced scarring on their heart, were able to bounce back and, by the time they reached adolescence, had no scarring. He wondered if it was because the babies’ own heart stem cells were able to repair the damage.

Scarring is a common side effect of a heart attack and affects the ability of the heart to be able to pump blood efficiently around the body. As a result of that diminished pumping ability people have less energy, and are at increased risk of further heart problems. For years it was believed this scarring was irreversible. This study, published in the Journal of Cardiovascular Translational Research, suggests it may not be.

Westaby and his team implanted what they describe as a “novel mesenchymal precursor (iMP)” type of stem cell in the hearts of patients who were undergoing heart bypass surgery following a heart attack. The cells were placed in parts of the heart that showed sizeable scarring and poor blood flow.

Two years later the patients showed a 30 percent improvement in heart function, a 40 percent reduction in scar size, and a 70 percent improvement in quality of life.

In an interview with the UK Guardian newspaper, Westaby admitted he was not expecting such a clear cut benefit:

“Quite frankly it was a big surprise to find the area of scar in the damaged heart got smaller,”

Of course it has to be noted that the trial was small, only involving 11 patients. Nonetheless the findings are important and impressive. Westaby and his team now hope to do a much larger study.

CIRM is funding a clinical trial with Capricor that is taking a similar approach, using stem cells to rejuvenate the hearts of patients who have had heart attacks.

Fred Lesikar, one of the patient’s in the first phase of that trial, experienced a similar benefit to those in the English trial and told us about it in our Stories of Hope.

Taking Steps Toward Personalized Heart Transplants

Over five million Americans have heart failure (HF), a condition in which the heart muscles become too weak to pump an adequate amount of blood, oxygen and nutrients to the body’s other organs. People with heart failure suffer from shortness of breath, chronic weakness and a fifty percent chance of dying within the first five years of diagnosis.

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Heart failure weakens the heart’s ability to pump blood to the body.
Image credit: Fran Milner, http://www.franimation.com

Heart transplants: swapping one disease for another
The only true cure for heart failure is an organ transplant but donor organs are in limited supply. And those lucky enough to receive a transplant need to take life long immunosuppressive drugs to fight off organ rejection, which often leads to other serious health problems like risk of infection, high blood pressure, diabetes and kidney failure.

It’s not a pretty picture for patients and with a cost to the nation of $32 billion annually, heart failure affects us all.

In a recent Circulation Research journal article, a team at the Massachusetts General Hospital (MGH) Center for Regenerative Medicine (CRM) reported on an incremental yet important step toward an alternative approach to heart transplants: growing bioengineered hearts with a patient’s own stem cells.

Bioengineered hearts: been there, done that
Bioengineered hearts may sound far fetched but eight years have already passed since researchers showed it’s possible with animal models. In that 2008 study, scientists at the University of Minnesota soaked rat hearts in detergents that cleaned away all of the heart cells, leaving behind a scaffold of connective tissue that is secreted by the cells. They then “re-seeded” the scaffold with rat progenitor heart muscle cells. Incredibly, after 4 days in a bioreactor, the tissue began contracting. After 8 days, using electrical stimulation, the hearts could pump with measurable strength.

heartscaffold

Custom built bioreactor with a partially recellularized human whole-heart cardiac scaffold. Image credit: Bernhard Jank, MD, Ott Lab, CRM MGH

Harald Ott, the first author of that proof of concept study, now leads the MGH team in the current study. With an eye toward bringing this method to the clinic, Ott aimed to reproduce the rat studies using human cells and hearts. Specific consent was obtained to recover seventy-three human hearts donated after brain death or cardiac death and were determined to be unusable for clinical transplant.

Just as in the previous study, heart scaffolds were created by clearing away the cells from these organs. Half a billion human heart muscle cells, or cardiomyocytes, that had been grown from human induced pluripotent stem cells (iPS) were then injected into the scaffolds. At this early stage of research, the team did not attempt to reseed the entire heart but specifically focused on areas around the left ventricle – the heart chamber responsible for pumping oxygenated blood out to the rest of the body.

In order to recellularize the scaffold under conditions that resemble the contractions that actually occur in a human heart inside the body, pressure was rhythmically applied using a balloon inside the ventricle – watch it in action by downloading this video.

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Decellularized heart scaffold is injected with iPS heart muscle cells and incubated in a bioreactor to grow new heart muscle (Circ Res. 2016;118:56-72).

After incubating the heart for 14 days in a bioreactor, the team confirmed the cardiomyocytes had formed into functioning heart muscle, or myocardial, tissue that contracted upon electrical stimulation (watch the beating heart by downloading this video).

Looking ahead to a “grow yourself a new heart” future
These results set a course for a future in which scientists could grow a new, personalized heart for people with heart failure. Since the bioengineered heart would be built using iPS cells derived from the patient’s own skin or blood sample, this technique would likely get around the problems of organ rejection and the need for immunosuppressive drugs. Additional analysis in the current study also confirmed that the donor heart scaffold itself, which is void of cells, probably will not pose tissue rejection problems either.

The other key problem, a limited supply of donor hearts, was also addressed. Heart scaffolds donated after cardiac death performed just as well as those donated after brain death which would make this technique available to more patients waiting anxiously for a transplant.

The MGH team would be the first to tell you this “grow yourself a new heart” scenario is still off on the horizon. But as first author, Jacques Guyette, stated in a news release, there are milestones to reach along the way:

“Regenerating a whole heart is most certainly a long-term goal that is several years away, so we are currently working on engineering a functional myocardial [heart muscle tissue] patch that could replace cardiac tissue damaged due a heart attack or heart failure.”

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A new way to make heart stem cells could potentially repair the damage of heart disease

Today we’re going to talk about heart failure. It’s a sobering topic given that over 20 million people world wide are currently suffering from this disease. Heart failure happens when the body’s heart can no longer pump blood effectively, which can lead to many nasty side effects and inevitably hastens death.

Typical strategies for treating heart failure focus on managing symptoms and delaying disease progression. But for patients, many of whom are elderly, a life of chronic management and frequent hospital stays is daunting. They deserve better.

Here’s where stem cell research could provide new treatments for heart failure. Some stem cells can be coaxed into new heart tissue that could repair damage and restore heart function. While other types of stem cells can release factors that facilitate the development of new blood vessels or that reduce tissue scarring, both of which improve heart function. Some of these treatments are being tested in clinical trials (for instance CIRM is funding a stem cell trial for heart disease sponsored by Capricor Therapeutics), although none have been approved yet.

But there’s good news on this front. Today, the Gladstone Institutes published a study in Cell Stem Cell describing a new method for making transplantable heart stem cells that improved heart function in mice and could potentially treat heart failure in humans.

A new method for making transplantable heart stem cells

The goal of the Gladstone study was to generate a specific type of heart stem cell called a cardiovascular progenitor cell that could survive and develop into the different types of mature heart cells to improve heart function when transplanted into mice.

Using technology previously developed in the lab of Gladstone Professor Sheng Ding, the team used a cocktail of chemicals to turn skin cells into cardiac progenitor cells (CPCs). These cells are like stem cells but specific to the heart and thus can only make heart cells. The CPCs they made had two important qualities: they could be expanded in a culture dish for multiple generations and they could develop into the three main types of adult heart cells (cardiomyocytes, endothelial cells and smooth muscle cells) that are required for heart regeneration.

Scientists made a new type of heart stem cell that can turn into the three main types of adult heart cells. (Image: Yu Zhang)

Gladstone scientists made a new type of heart stem cell that can make the three main types of adult heart cells. (Image: Yu Zhang)

Because of their ability to replicate and to become adult heart cells, they named these cells induced expandable cardiovascular progenitor cells or ieCPCs. They transplanted ieCPCs in mice that had suffered a heart attack and were pleased to see that 90% of engrafted cells (the ones that survived and stuck around) developed into functioning heart cells that worked seamlessly with the existing heart cells to improve the damaged heart’s ability to pump blood. From a single injection of one million ieCPCs, the improvements in heart function lasted for three months.

In a Gladstone News Release, first author on the study, Yu Zhang, explained why ieCPCs are better for transplantation into damaged hearts than adult heart cells like cardiomyocytes or the muscle cells of the heart:

“Scientists have tried for decades to treat heart failure by transplanting adult heart cells, but these cells cannot reproduce themselves, and so they do not survive in the damaged heart. Our generated ieCPCs can prolifically replicate and reliably mature into the three types of cells in the heart, which makes them a very promising potential treatment for heart failure.”

Another benefit to ieCPCs was that they did not generate tumors when transplanted. This can happen with non-heart stem cells or with cells derived from pluripotent stem cells.

What does the future hold for ieCPCs?

A heart attack can kill more than one billion heart cells, and while the heart has some regenerative ability, it cannot replace that many cells on its own. The Gladstone study is exciting because it provides a new population of heart stem cells that can be expanded in a dish to generate a large donor population of stem cells for transplantation.

Senior author Shen Ding spoke to the robustness of their new stem cell technology:

Sheng Ding

Sheng Ding

“Cardiac progenitor cells could be ideal for heart regeneration. They are the closest precursor to functional heart cells, and, in a single step, they can rapidly and efficiently become heart cells, both in a dish and in a live heart. With our new technology, we can quickly create billions of these cells in a dish and then transplant them into damaged hearts to treat heart failure.”

Additionally, their new method opens the doors for generating patient-specific stem cell treatments.

“Because these cells are generated from skin cells, it opens the door for personalized medicine, using a patient’s own cells to treat their disease.”

Sheng Ding’s lab is one to watch if you follow research in stem cell biology and regenerative medicine. We recently blogged about a different but equally important study from his lab where he made functional pancreatic beta cells from skin as a potential cell therapy for diabetes. I hope that his team will ultimately be able to translate their current research in both diabetes and heart disease towards clinical applications in humans.

UCLA Study Suggests New Way to Mend a Broken Heart

When you suffer a heart attack, your heart-muscle cells become deprived of oxygen. Without oxygen, the cells soon whither and die—and are entombed within scar tissue. And once these cells die, they can’t be brought back to life.

But maybe—just maybe—there is another way to build new heart muscle. And if there is, scientists like Dr. Arjun Deb at the University of California, Los Angeles (UCLA), are hot on the trail to find it.

Scar forming cells (in red) in a region of the injured heart expressing blood vessel cell marker in green and thus appearing yellow (see arrows). This study observed that approximately a third of the scar-forming cells in the injured region of the heart adopted "blood vessel" cell-like characteristics. [Credit: Dr. Arjun Deb/Nature]

Scar forming cells (in red) in a region of the injured heart expressing blood vessel cell marker in green and thus appearing yellow (see arrows). This study observed that approximately a third of the scar-forming cells in the injured region of the heart adopted “blood vessel” cell-like characteristics. [Credit: Dr. Arjun Deb/Nature]

Published yesterday in the journal Nature, Deb and his team at UCLA’s Eli & Edythe Broad Center for Regenerative Medicine and Stem Cell Research have found some scar-forming cells in the heart have the ability to become blood vessel-forming cells—if given the proper chemical ‘boost.’

“It is well known that increasing the number of blood vessels in the injured heart following a heart attack improves its ability to heal,” said Deb. “We know that scar tissue in the heart is associated with poor prognosis. Reversing or preventing scar tissue from forming has been one of the major challenges in cardiovascular medicine.”

Tackling the ever-growing problem in heart disease can seem an almost insurmountable task. While heart disease claims more lives worldwide than any other disease, advances in modern medicine in recent decades mean that more and more people are surviving heart attacks, and living with what’s called ‘heart failure,’ for their hearts can no longer beat at full capacity, and they have trouble taking long walks or even going up a flight of stairs.

Transforming this scar tissue into functioning heart muscle has therefore been the focus of many research teams, including CIRM grantees such as Drs. Deepak Srivastava and Eduardo Marbán, who have each tackled the problem from different angles. Late last year, treatment first designed by Marbán and developed by Capricor Therapeutics got the green light for a Phase 2 Clinical Trial.

In this study, Deb and his team focused on scar-forming cells, called fibroblasts, and blood-vessel forming cells, called endothelial cells. Previously, experiments in mice revealed that many fibroblasts literally transformed into endothelial cells—and helped contribute to blood vessel formation in the injured area of the heart. The team noted this phenomenon has been called the mesenchymal-endothelial transition, or MEndoT.

In this study, the researchers identified the molecular mechanism behind MEndoT—and further identified a small molecule that can enhance this transition, thus boosting the formation of blood vessels in the injured heart. This study bolsters the idea of focusing on the creation of blood vessels as a way to help reverse damage caused by a heart attack. Said Deb:

“Our findings suggest the possibility of coaxing scar-forming cells in the heart to change their identity into blood vessel-forming cells, which could potentially be a useful approach to better heart repair.”