Heart Attack Recovery With Stem Cells?

U.S. Study: Stem cells can regenerate heart tissue after heart attack. When someone has a heart attack, great slabs of muscle tissue die and many vessels are destroyed. Up to 40 percent of heart tissues die, and dead muscle is replaced by scar, not newly formed muscle.

The heart is a muscle that pumps blood to the body’s organs, and when scar tissue forms, it can’t contract properly. This predisposes heart attack survivors to arrhythmias, enlargement of the heart, heart failure and death.

Doctors often try to reduce or compensate for the damage by giving drugs to protect this muscle from working too hard. Often, though, heart failure ultimately sets in, requiring mechanical support from a pump or even a heart transplant.

But because stem cells have the power to generate new cells, therapy using these types of cells poses the possibility that the heart can be healed from inside out: damaged or diseased heart cells can be regenerated and new muscle tissue will grow to replace the damaged one.

This approach has been tested by scientists a few times since 2007, many times in lab mice and at least twice in human trials. One human trial was done in 2007 on 60 heart patients in the United Kingdom by researchers from the University of Bristol and the Bristol Heart Institute. Another was a phase I clinical trial conducted in 2009 on 53 heart attack survivors from 10 cardiac centers across the United States.

Both trials, which showed that adult stem cells may help repair heart tissue damaged by heart attack, made use of mesenchymal stem cells (MSC) that were harvested from the bone marrow of healthy adult donors.

But that method runs the risk of donor cells being rejected by the immune system of recipients.

Considering this, researchers from the University of California in San Francisco have tested a new approach for treating damaged cardiac tissue following a heart attack using patients’ own stem cells taken from their hearts.

Early experiments on mice suggest that this novel strategy could potentially improve cardiac function, minimize scar size, lead to the development of new blood vessels—and avoid the risk of tissue rejection. Their findings were reported online in the journal PLoS ONE.

The UCSF researchers say their study breaks ground and is the first step to a future where patients who have severe heart failure after a heart attack or have cardiomyopathy would be able to be treated with their own cardiac stem cells to improve the overall health and function of the heart.

Unlike transplants of organs or stem cells from donors, there would be no concern of cell rejection after therapy because the cells would have come from the patients themselves.

In their investigation, researchers isolated and characterized a novel type of cardiac stem cell from the heart tissue of middle-aged mice following a heart attack.

“These findings are very exciting,” said first author Dr. Jianqin Ye, senior scientist at UCSF’s Translational Cardiac Stem Cell Program. First, “we showed that we can isolate these cells from the heart of middle-aged animals, even after a heart attack.” Second, he said, “we determined that we can return these cells to the animals to induce repair.”

For their investigation, the researchers conducted two experiments:

In the first, they placed the cardiac stem cells into a Petri dish and showed they had the ability to differentiate into the three cells of the heart—cardiomyocytes or “beating heart cells,” endothelial cells and smooth muscle cells.

In the second, they made copies or “clones” of the cells and grafted them into the tissue of other mice that shared the same genetic background as those that suffered heart attacks. In the mice, the cells induced blood vessel growth (angiogenesis) and differentiated into endothelial and smooth muscle cells. Overall, the cells were able to improve cardiac function.

According to Dr. Ye, the stem cells were identified and isolated in all four chambers of the heart. This means that they can potentially be isolated them from patients’ hearts by doing right ventricular biopsies, he said, the procedure that is “the safest way of obtaining cells from the heart of live patients, and is relatively easy to perform.”

Discovery: sSa-1+ stem cells
The cells used by Dr. Ye’s and Dr. Yeghiazarian’s team are known as Sca-1+ stem enriched in Islet (Isl-1), which express cardiac precursors and play a major role in cardiac development.

Until now, most research has focused on a different subset of cardiac progenitor, or early stage, cells known as, c-kit cells.

Like the c-kit cells, the Sca-1+ cells are located within a larger clump of cells called cardiospheres.

The UCSF researchers used special culture techniques and isolated Sca-1+ cells enriched in the Isl-1expressing cells—believed to be instrumental in the heart’s development. Since Isl-1 is expressed in the cell nucleus, it has been difficult to isolate them but with the new technique the researchers were able to enrich the Sca-1+ in this cell population.

Because “most of the previous research has focused on a different subset of cardiac progenitor cells,” observes senior author Dr. Yerem Yeghiazarians, director of UCSF’s Translational Cardiac Stem Cell Program and an associate professor at the UCSF Division of Cardiology, “The finding extends the current knowledge in the field of native cardiac progenitor cell therapy.”

“These novel cardiac precursor cells appear to have great therapeutic potential,” he adds.

Dr. Yeghiazarians says the findings suggest a potential treatment strategy.

“Heart disease, including heart attack and heart failure, is the number one killer in advanced countries,” he notes. “It would be a huge advance if we could decrease repeat hospitalizations, improve the quality of life and increase survival,” he says, adding that more studies are being planned to address these issues in the future.

Heart disease is the leading killer, not only in advanced countries, but also in the world. One out of every three deaths in the U.S. is caused by either a heart attack or a stroke, the American Heart Association says. This year, around 800,000 Americans will have a new heart and more than half that number will have a recurrent one.

Today, people in developing countries aren’t spared what used to be known as the “disease of the wealthy.” The World Health Organization estimates that in 2008, about 17.3 million people died from cardiovascular diseases—and a huge chunk of that came from heart disease, with over 80 percent of these deaths taking place in low- and middle-income countries.

The financial costs are also huge. In the U.S. alone, the medical costs of cardiovascular disease are projected to triple from US$272.5 billion to US$818.1 billion between now and 2030, according to a report published in the journal Circulation.

The study was funded by the Wayne and Gladys Valley Foundation, the UCSF Cardiac Stem Cell Fund and the Harold Castle Foundation.

It was a collaborative effort of UCSF research centers: the UCSF Division of Cardiology, the Division of Cardiology, the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, the Cardiovascular Research Institute, the Department of Pediatrics, the Department of Anesthesia and Perioperative Care and the Department of Cell and Tissue Biology.

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