A New Procedure to Make Induced Pluripotent Stem Cells


In order to use human pluripotent stem cells, they must match the tissue types of the patient. Otherwise the patient’s immune system will reject any implanted cells, unless they are administered into areas of the body outside the long reach of the immune system like the eye or the brain.

However, induced pluripotent stem cells (iPSCs) are made from the patient’s own cells, by using a combination of genetic engineering and cell culture techniques and any cells that differentiated from an established iPSCs line will match the tissue types of the patient and not be rejected. Unfortunately, iSPCs take a while to make and the quality of the cell line varies from person to person. Therefore, using these cells in a clinical setting represents some issues.

A new technique that was developed at the EURAC Center for Biomedicine simplifies the method for iPSC derivation from blood cells. Instead of having to use specific reagents to isolated white blood cells, which contain a nucleus and DNA, from red blood cells, which have no nucleus. the EURAC Center for Biomedicine method does not require such reagents. This reduces cost, the time required to derive iPSCs, and the complexity of the procedure. The new EURAC Center for Biomedicine protocol will also work well on blood samples that were previously collected and preserved by freezing in a blood bank. Because it is highly convenient to store samples in this fashion, this technique is highly feasible.

This technique uses no viruses, and can readily make iPSCs to study illnesses in the laboratory. Alessandra Rossini and her colleagues succeeded in making iPSC lines from several different patients with a variety of maladies. This technique might revolutionize iPSC-making protocols.

Making Connections Between Neural Structures in Culture


Even though it is now possible to fabricate organs and tissues in the laboratory, the vast majority of these structures can be made in isolation without compromising their functionality. Brain cells are quite different, since they required connections known as synapses with other brain cells. Synapses are also responsible for the functional interactions between different regions of the brain. Even though nerve cells (neurons) can be made in the laboratory, engineering connections between neurons is not trivial. Furthermore, some laboratories have used pluripotent stem cells to make portions of the brain in the laboratory, but getting those portions to properly connect with other regions of the brain has proven stultifying.

A new study by William Freed at the National Institutes of Health and his colleagues has designed a way to successfully grow multiple brain structures in the laboratory that form proper connections with each other in culture. This report is the first of its kind.

In particular, Freed and his co-workers defined a culture system for human pluripotent stem cells that produced connected human midbrain and neocortex.

The midbrain houses dopaminergic neurons (mDAs). These neurons use the neurotransmitter dopamine to signal to other neurons that reside elsewhere in the brain. Abnormalities of mDAs or connections between mDAs and other neurons are thought to play intimate roles in disorders like schizophrenia, Parkinson disease, attention-deficit disorder, Roulette’s syndrome, Lesch-Nyhan syndrome, and maybe even eating disorders.

Unfortunately, studying neocortical neurons and mDAs in isolation reveal little about the connections between them or their interactions. However, this new data from Freed that shows that it is possible to grow and interconnect these two types of neurons in culture provides neuroscientists with a powerful model system for examining this system and the abnormalities that afflict it.

The encourage connections between the two neuronal populations, mDAs and neocortical neurons were grown in special containers called “ibidi wound healing” dishes. Ibidi wound healing dishes contain two chambers separated by a removable barrier. Neocortical neurons were grown on one side and mDAs were grown on the other side. Both neuron populations were derived from human pluripotent stem cells. Once the cell cultures had properly formed, the barrier was removed and the two cell populations formed synapses across the barrier.

Freed is eager to examine human pluripotent stem cells derived from patients with neurological disorders that have been traced to abnormalities with connections between mDAs and other neuronal populations to study if neurons made from these patient’s cells properly synapse.

Clearly, this model system has great potential. This work was published in Restorative Neurology and Neuroscience, 2015 DOI: 10.3233/RNN-1140488.

Bioengineered Nanofiber Patch to Treat Heart Failure


Stem cells have the capacity to heal damaged tissues and replace death cells. However, harvesting and employing the right stem cell for the right job, at the right dose, and under the right conditions has proven to be a difficult puzzle to solve.

In particular, the damaged heart has proven rather difficult to heal with stem cells. Many different clinical trials have administered stem cells by direct injection, intracoronary delivery in coronary vessels, or injection into the surface of the heart. These studies have examined the efficacy of stem cells from fat, bone marrow, the heart itself, and other sources. The upshot of these studies is that some strategies work and others do not, but even those that work only work modestly well.

The biggest obstacle is overcoming the hostile environment into which stem cells are introduced when they are administered into the heart after a heart attack. The post-heart attack heart suffers from lots of inflammation, low oxygen concentrations, and the pervasive presence of dangerous molecules. Several laboratories have discovered that preconditioning stem cells by growing them in low-oxygen culture conditions can increase their survival in the post-heart attack heart as can genetically engineering cells to resist increased levels of cell stress. Now, a research team from Ohio State University has designed a different strategy to beat the hostility of the post-heart attack heart.

After a heart attack, oxygen-deprived tissues die and various chemical messengers instruct damaged cells to die. However, data from a host of clinical trials strongly suggests that this dangerous time is the best time to introduce stem cells into the heart. Thus, this window of opportunity is the “best of times and the worst of times” for cell therapy.

As it turns out, about 30% of all mammalian protein-encoding genes are regulated by small molecules called microRNAs (miRNAs). MiRNAs are single-stranded RNA molecules approximately 22 nucleotides in length that bind to messenger RNAs and regulate their translation into protein or half-life. Research has shown that miRNAs have substantial potential as a therapeutic target for the treatment of many diseases, including cardiovascular disease. A good deal of research in laboratory animals and in cultured heart cells that altered expression of miRNAs such as miR-1, miR-133, miR-21 and miR-208 contribute to the development of heart disease. The laboratory of Mahmood Khan, a scientist at the Davis Heart and Lung Research Institute at The Ohio State University Wexner Medical Center, has focused on miR-133a which seems to play a role in slowing fibrosis and cardiac remodeling. Importantly, levels of miR-133a are reduced in the heart tissues of patients who have suffered a heart attack.

Khan and his group predicted that increasing the levels of miR-133a in stem cells as they are cultured might preprogram the cells to survive in the hostile environment of the post-heart attack heart.

Khan’s team began by bioengineering a molecule to induce mesenchymal stem cells (MSCs) to produce miRNA-133a. When transplanted into an animal model of cardiac ischemia, the pre-treated MSCs showed improved survival over non-treated MSCs. These pre-treated MSCs also did a better job at decreasing the global damage to the heart, and increasing the thickness of the left ventricle, the main pumping chamber of the heart.

“We found that the pre-treated MSCs did a better job at decreasing the global damage to the heart, along with improvement in the left-ventricular wall thickness compared to the untreated MSCs,” said Dr. Angelos. “MSCs are a commonly used cell type in current heart failure studies, so our findings are definitely relevant to that work.”

The results of these experiments were published in the March issue of the Journal of Cardiovascular Pharmacology.

While trying to increase cell survival, Khan and his colleagues also addressed the problems surviving stem cells face in the heart – how to help them function along existing heart tissue without getting in the way or fouling things up.

To date, most stem cells are grown in flat culture plates and either injected directly into the heart muscle (typically on the periphery of scar tissue), or infused into the heart via an artery. While most of these stem cells either die or diffuse throughout the body, successfully transplanted stem cells sometimes inadvertently disrupt heart function.

“The heart is a constantly moving, connected matrix of muscle fibers working together to make the heart pump in sync,” said Dr. Angelo’s, an emergency medicine researcher and collaborator of Dr Khan. “Transplanted stem cells may not align with native tissue, potentially disrupting or attenuating signals that keep a steady heartbeat. There’s evidence that this could contribute to arrhythmias.”

To create a more secure environment that allows implanted stem cells successfully engraft into the heart, Drs. Khan and Angelos have used a biodegradeable nanofiber “patch” seeded with human inducible pluripotent stem cells derived cardiomyocytes (hiPSC-CMs). Khan and Angelos chose hiPSC-CMs because these cells are patient derived and can be used to model the heart disease of patients and for autologous stem cell transplantation in patients with failing hearts.

Both aligned nanofiber patch and standard culture plate were seeded with hiPSC-CMs. Both sets of cultures heart muscle cells were compared for calcium signaling (a measure of proper heart muscle function) and synchronous beating. Within two weeks, both stem cell cultures were spontaneously beating like a miniature heart, but the linear grain of the nanofiber formed an aligned pattern of cells that looked and functioned like a healthy heart tissue.

“The cardiomyocytes cultured on a flat plate are scattered and disorganized. Cardiomyocytes grown on the nanofiber scaffolding look more like healthy heart cells, beat more strongly and in greater synchronicity than cells from the flat plate,” said Dr. Khan. “Next, we hope to use what we’ve learned from this study to develop a thicker, multi-layer patch that could help restore thin and weakened heart walls.”

Drs. Khan and Angelos see great potential future clinical applications for their nanofiber bandage. This treatment could potentially bandage the damaged heart muscle of heart patients with the nanofiber cardiac patch. Also, it is possible that they could someday combine the microRNA pre-treatment technique and the patch to give stem cells a survival boost along with a protective structure to improve outcomes.

Khan, his co-workers and his collaborators published this work on May 19 in PLoS ONE.

New Tissue Engineering Technique Could Lead to Growing Larger Organs in the Laboratory


Tissue engineers from the Universities of Liverpool and Bristol have invented a novel tissue “scaffold” technology that might one day enable the growth large organs in the laboratory.

According to data generated by these experiments, it is possible to combine cells with a special scaffold to produce living tissues in the laboratory. Hopefully, such organs can then be implanted into patients who need to have a diseased body part replaced. To this point, growing large organs in the laboratory has been impossible because growing larger structures in the laboratory limits the delivery of oxygen supply to the cells in the center of the organ. Therefore, growing tissues in the laboratory has been restricted to small structures that are readily served by the diffusion of oxygen.

In the experiments conducted by the University of Liverpool and Bristol teams, cartilage tissue engineering was employed as a model system for testing strategies for overcoming the oxygen limitation problem.

They manufacture a new class of artificial membrane binding proteins that attached to stem cells. Then they attached to these cell surface proteins the oxygen-carrying protein, myoglobin, before they used the cells to engineer cartilage. Since myoglobin is an oxygen-storage molecule, it will bind oxygen and provide a reservoir of oxygen for cells that cells can access when the oxygen in the scaffold drops to dangerously low levels.

Professor Anthony Hollander, Head of the University of Liverpool’s Institute of Integrative Biology, said: “We have already shown that stem cells can help create parts of the body that can be successfully transplanted into patients, but we have now found a way of making their success even better. Growing large organs remains a huge challenge but with this technology we have overcome one of the major hurdles. Creating larger pieces of cartilage gives us a possible way of repairing some of the worst damage to human joint tissue, such as the debilitating changes seen in hip or knee osteoarthritis or the severe injuries caused by major trauma, for example in road traffic accidents or war injuries.”

These results could expand the possibilities in tissue engineering, not only in cartilage, but also for other tissues such as cardiac muscle or bone. This new methodology in which a normal protein is converted into a membrane binding protein to which helpful molecules can be attached, is likely to pave the way for the development of a wide range of new biotechnologies.

Dr Adam Perriman, from the University of Bristol, added: “From our preliminary experiments, we found that we could produce these artificial membrane binding proteins and paint the cells without affecting their biological function. However, we were surprised to discover that we could deliver the necessary quantity to the cells to supplement their oxygen requirements. It’s like supplying each cell with its own scuba tank, which it can use to breathe from when there is not enough oxygen in the local environment.”

Previous work by Hollander’s group includes the development of a method of creating cartilage cells from stem cells. This method helped make the first successful transplant of a tissue-engineered trachea, which utilized the patient’s own stem cells, possible.

This work appeared in the paper, “Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue,” which was published in Nature Communications.

Using Drugs to Stimulate your Own Stem Cells to Treat Multiple Sclerosis


Paul Tesar from Case Western Reserve in Cleveland. Ohio and his colleagues have discovered that two different drugs, miconazole and clobetasol, can reverse the symptoms of multiple sclerosis in laboratory animals. Furthermore, these drugs do so by stimulating the animals’ own native stem cell population that insulates nerves.

Multiple sclerosis (MS) is a member of the “demyelinating disorders.” The cause of MS remains unknown, but all of our available evidence strongly suggests that MS is an autoimmune disease in which the body’s immune system attacks its own tissues. In MS the immune system attacks and destroys myelin — the fatty substance that coats and protects nerve fibers in the brain and spinal cord. We can compare myelin to the insulation that surrounds electrical wires. When myelin is damaged, the nerve impulses that travel along that nerve may be slowed or blocked.

The myelin sheath is made by cells known as “oligodendrocytes,” and oligodendrocytes are derived from a stem cell population known as OPCs, which stands for oligodendrocyte progenitor cells. If this stem cell population could be stimulated, then perhaps the damaged myelin sheath could be repaired and the symptoms of MS ameliorated.

In a paper that appeared in the journal Nature (522, 2015 216-220), Tesar and the members of his research team, and his collaborators used a pluripotent mouse stem cell line and differentiated them into OPCs. Thyroid hormone is a known inducer of OPC differentiation. Therefore, Tesar and others screened a battery of drugs to determine if any of these compounds could induce OPC differentiation as cell as thyroid hormone. From this screen using cultured OPCs, two drugs, the antifungal drug miconazole and clobetasol, a corticosteroid of the glucocorticoid class, proved to do a better job of inducing OPC differentiation than thyroid hormone.

Was this an experimental artifact? Tesar and others devised an ingenious assay to measure the effectiveness of these two drugs. They used brain slices from fetal mice that were taken from animals whose brains had yet to synthesize myelin and applied OPCs to these slices with and without the drugs. With OPCs, no myelin was made because the OPCs did not receive any signal to differentiate into mature oligodendrocytes and synthesize myelin. However in the presence of either miconazole or clobetasol, the OPCs differentiated and successfully myelinated the brain slices.

Experiments in tissue culture are a great start, but do they demonstrate a biological reality within a live animal? To answer this question, Tesar and his crew injected laboratory mice with purified myelin. The immune systems of these mice generated a robust immune response against myelin that eroded the myelin sheath from their nerves. This condition mimics human MS and is called experimental autoimmune encephalitis, and it is an excellent model system for studying MS. When mice with experimental autoimmune encephalitis (EAE) were treated with either miconazole or clobetasol, the EAE mice showed a remarkable reversal of symptoms and a solid attenuation of demyelination. Tissue samples established that these reversals were due to increased OPC activity.

When the mechanisms of these drugs were examined in detail, it became clear that the two drugs worked through distinct biochemical mechanisms. Miconazole, for example, activated the mitogen-activated protein kinase (MAPK) pathway, but clobetasol worked through the glucocorticoid receptor signaling pathway. Both of these signaling pathways converge, however, to increase OPC differentiation.

Both miconazole and clobetasol are only approved for topical administration. However, the fact that these drugs can cross the blood-brain barrier and effect changes in the brain is very exciting. Furthermore, this work establishes the template for screening new compounds that might be efficacious in human patients.

In the meantime, human patients might benefit from a clinical trial that determines if the symptoms and neural damage caused by MS can be reversed by the administration of these drugs or derivatives of these drugs.

Treating Colon Cancer By Activating Damaged Genes


What if doctors could turn cancer cells into healthy cells? It would change everything about how we treat cancer. Researchers may have discovered a way to do that in colorectal cancer.

What if we could turn the clock back on cancer cells and return them to their healthy status?   A new study in animals might have accomplished exactly that.

A research team from the Memorial Sloan Kettering Cancer Center has reactivated a defective gene in mice with colorectal cancer.  This gene, adenomatous polyposis coli, or Apc, is commonly defective in colorectal cancer cells.  Approximately 90 percent of colorectal tumors have a loss-of-function mutation of this gene.

At the onset of this research project, The Sloan Kettering group suppressed the expression of the Apc gene in mice.  The Apc gene encodes a protein that regulates an important cell signaling pathway known as the Wnt signal pathway.  Suppression of Apc activates the Wnt signaling pathway, which helps cancer cells grow and survive.

Afterwards, they reactivated the Apc gene, which returned Wnt signaling to its normal levels and the cancerous tumors stopped growing, and normal intestinal function was restored in four days. By two weeks after Apc was reactivated, the tumors were gone and there were no lingering signs of no signs of cancer relapse during the six-month follow-up.

The same approach turned out to be effective in mice with colorectal cancer tumors that result from activating mutations in the Kras gene and loss-of-function mutations in the p53 gene.  In humans, about half of colorectal tumors have these mutations

This study was published in the prestigious international journal, Cell, by Scott Lowe and his colleagues.  “Treatment regimens for advanced colorectal cancer involve combination chemotherapies that are toxic and largely ineffective, yet have remained the backbone of therapy over the last decade,” said Lowe.

Apc reactivation might very well be the way to improved treatment for colorectal cancer.  It is doubtful it will be helpful in other types of cancer, but in the future, it might become so.  “The concept of identifying tumor-specific driving mutations is a major focus of many laboratories around the world,” said Lukas Dow, Ph.D., of Weill Cornell Medical College, who is the first author of this study.

“If we can define which types of mutations and changes are the critical events driving tumor growth, we will be better equipped to identify the most appropriate treatments for individual cancers,” said Dow.

Colorectal cancer begins in the colon or rectum, and it remains the second-most prevalent cause of cancer death in developed countries.

According to the Surveillance, Epidemiology, and End Results Program, in 2012, there were 1,168,929 people living with colon and rectal cancer in the United States.

Estimates postulate that there will be 132,700 new cases of colorectal cancer in the United States in 2015, and about 49,700 people will lose their lives to this disease. Worldwide, colorectal cancer is the cause of approximately 700,000 deaths each year.

Internist and gastroenterologist Dr. Frank Malkin expressed optimism regarding genetic research into colorectal cancer.  He said in an interview with the medical news service, Healthline: “They’ve identified a suppressor gene that can turn a tumor on and off. It can suppress the cancer and destroy it rapidly. That’s very promising.”

Cancers are normally treated with a combination of surgery, chemotherapy, and radiation.  These rather harsh treatments can take a lasting toll.  Easier and more effective treatments could change the lives of cancer patients.

Michelle Gordon, D.O., FACOS, FACS, finds it encouraging. “If this treatment is to be believed, all current modalities will be obsolete.”

However, Malkin and Gordon both cautioned that it is simply too early to bring this strategy to the clinic to treat human patients.

“There are so many unknowns when taking a mouse model to humans,” Gordon told Healthline. “This may be the foundational step that will lead to curing most colorectal cancers. This study can provide hope to future generations of colorectal cancer [patients], but I believe a cure is decades away.”

Researchers know Apc mutations initiate colorectal cancer, but they are unsure if Apc mutations are involved in promoting tumor growth after the cancer has developed.

The next step in this work will examine the ability of Apc reactivation to affect tumors that have spread or metastasized to distant locations in the body.  Lowe and his colleagues are also hard at work to determine precisely how Apc works.  That will help scientists develop safe treatments that change cancer cells into normal cells. Such a drug could make colorectal cancer treatment easier, faster, and safer.

How this research will impact other types of cancer remains unclear.  “Cure rates for colorectal cancers are better than they used to be, especially when treated in the early stages,” said Malkin.  Nevertheless, it is still far better to stop tumors before they start.

According to Malkin, the number of colon cancer cases has dropped dramatically since routine colonoscopy screening began. A colonoscopy allows doctors to find and remove polyps before they turn cancerous.  Malkin also looks forward to genetic research that will identify those at greater risk for colorectal cancers.

“Right now, we’re using colonoscopy to screen people over 50, most who don’t have the genetic predisposition and will never get colorectal cancer,” he said. “We don’t yet have the genetic studies that would help us identify high-risk patients so we don’t have to screen everyone.”

I must admit that I remain skeptical as to whether or not this will work.  The reasons for my skepticism lie in the fact that tumor cells in the colon are the result of a series of mutations in cells that cause the cells to overgrow and eventually become invasive.  Colorectal carcinoma cells have mutations in several genes and not just Apc.  Apc reactivation worked in these mice because this was the only gene affected in these animals.  In a cancerous human colon, the cancer cells have a variety of mutations.  Kurt Vogelstein’s work at Johns Hopkins has shown this in great detail.  If Lowe could demonstrate the efficacy of his treatment in mice with humanized immune systems that have been infected with human colorectal carcinoma cells, then I will believe that this technique could work in human patients.  For now, I remain skeptical.

Temple University Lab Shows Exosomes from Stem Cells Heal Hearts After a Heart Attack


Temple University stem cell researcher Raj Kishore, who serves as the Director of the Stem Cell Therapy Program at the Center for Translational Medicine at Temple University School of Medicine (TUSM), and his colleagues have used exosomes from stem cells to induce tissue repair in the damaged heart. The results of this fascinating research made the cover of the June 19, 2015 edition of the leading cardiovascular research journal, Circulation Research.

“If your goal is to protect the heart, this is a pretty important finding,” Dr. Kishore said. “You can robustly the heart’s ability to repair itself without using the stem cells themselves. Our work shows a unique way to regenerate the heart using secreted vesicles from embryonic stem cells.” Kishore’s group is in the early stages of characterizing the molecules in these exosomes that are responsible for inducing and potentiating tissue repair.

The heart beats throughout the lifetime of an individual. Despite its apparent constancy, the heart possess little to no ability to repair itself. When heart muscle is damaged in a heart attack, the heart is unable to replace the dead tissue and grow new contracting heart muscle. Instead, after a heart attack, it compensates for lost pumping ability by enlarging, a phenomenon known as ”remodeling.” .Remodeling, however, come with a high price, since the heart grows beyond the ability of the sparse cardiac circulatory system to properly convey blood to the enlarged heart muscle. Consequently, heart contraction weakens, leading to a condition known as congestive heart failure, which contributes to, or causes one in nine deaths in the United States. Heart disease is our nation’s leading killer.

Given the fact that heart disease is the result of the death of heart muscle cells, this condition seems to tailor-made for stem cell therapy. A variety of animal experiments with stem cells from bone marrow, muscle, fat, or embryos have shown that stem cells can regenerate heart muscle. However, the regeneration of the heart is much more complicated than was originally thought. For example, injecting damaged hearts with stem cells turned out to be a rather ineffective strategy because the heart, after a heart attack, is a very hostile place for newly infused cells. Dr. Kishore noted, “People know if they inject hundreds of stem cells into an organ, you’re going to be very lucky to find two of them the next day. They die. It’s as though you’re putting them into the fire and the fire burns them.”

Dr. Kishore has used a very different approach for regenerative medicine. Over 10 years ago, cancer researchers discovered tiny sacks excreted by cells that they called “exosomes.” These exosomes were thought to be involved with waste disposal, but later work showed that they were more mini-messengers, carry telegrams between cells. Exosomes proved to be one way a primary tumor communicated with distant metastases. Researchers later discovered that nearly all cell types excrete exosomes. Dr. Kishore and his team began to study the exosomes of stem cells to determine if these small vesicles could solve the heart-repair problem.

In 2011, Kishore’s team published the first paper to ever examine stem cell exosomes and heart repair. This paper established Kishore and his research team as a pioneer in exosome research and in the use of exosomes in the treatment of heart disease. A year after that paper, there were a total of 52 papers published on exosomes, but today there are 7,519 papers reporting on exosome research. Among those studies, only 13 or 14 have examined exosomes in heart disease. This new paper by Dr. Kishore’s team marks its third contribution to the science of exosomes and heart repair.

In the current study, Kishore and others used a mouse model of heart attack. Also involved in the research are Dr. Kishore’s colleagues from Temple’s Center for Translational Medicine, the Cardiovascular Research Center, and the Department of Pharmacology, as well as researchers from the Feinberg Cardiovascular Research Institute at Northwestern University in Chicago.

In this study, after suffering a heart attack, the mice received exosomes from either embryonic stem cells or exosomes from fibroblasts. Mice that received the fibroblast-derived exosomes served as the control group. The results were unmistakable. Mice that received exosomes from embryonic stem cells showed significantly improved heart function after a heart attack compared to the control group. More heart muscle cells in these mice survived after the heart attack, and their hearts also exhibited less scar tissue. Fewer heart cells committed suicide — a process known as programmed cell death, or apoptosis. Also, hearts from mice treated with embryonic stem cell-derived exosomes showed greater capillary development around the areas of injury. The increased density of blood vessels improved circulation and oxygen supply to the heart muscle. Further, there was a marked increase in endogenous cardiac progenitor cells, which is the hearts own internal stem cell population. These cells survived and created new heart cells. The heartbeat was more powerful in the experimental group compared to the control group, and the kind of unhealthy enlargement that compensates for tissue damage was minimized.

Vishore’s group also tested the effect of one of the most abundant gene-regulating molecules (microRNAs) found in the stem cell exosome; a microRNA called miR-294. When purified miR-294 alone was introduced to cardiac stem cells in the laboratory, it mimicked many of the effects seen when the entire exosome was delivered. “To a large extent, this micro-RNA alone can recapitulate the activity of the exosome,” Dr. Kishore said. “But we can never say it is responsible for all of the response because embryonic stem cell exosomes have many other microRNAs.”

Future research will examine both exosome therapy and the use of specific microRNAs for heart repair in large-animal models of heart attack with a view to eventually testing these components in human patients in clinical trials.

“Our work shows that the best way to regenerate the heart is to augment the self-repair capabilities and increase the heart’s own capacity to heal,” Dr. Kishore said. “This way, we’re avoiding risks associated with teratoma formation and other potential complications of using full stem cells. It’s an exciting development in the field of heart disease.”