Tuesday, December 6, 2016

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These photomicrograph cardiac stem cells isolated from mouse hearts clustered together in the shape of a heart.

Healing Broken Hearts

Can science unlock the secret of the heart's regenerative powers?
By Coleen L. Geraghty

Wounds mend, broken bones heal, but the human heart, once damaged by stroke or cardiac arrest, defies repair. Such was accepted scientific fact. Until now.

Within the last 10 years, researchers have uncovered evidence of the heart’s ability to heal itself – with a little help from friends. The ramifications are enormous. Temporary fixes such as heart transplants and drug therapy may yield to non-invasive treatments that restore heart muscle damaged during cardiac arrest.

“We’ve moved from thinking that heart cell regeneration was impossible to a new realization that is revolutionizing the way we approach treating heart disease,” said Mark Sussman, a biology professor at San Diego State University and member of the SDSU Heart Institute.

In Sussman’s lab, master’s, doctoral and post-doctoral students study molecular signaling and stem cell transplantation as they relate to heart disease. Their pioneering research augurs a day when stem cells will be used to regenerate and repair damage caused by a heart attack.

Replacing lost cells

Heart disease remains the number one killer of Americans. According to the Centers for Disease Control, nearly 700,000 people in the United States die from heart disease each year, about 29 percent of all deaths recorded annually.

The causes are myriad but doctors and biologists know that a heart attack occurs when coronary arteries become blocked, cutting off the supply of oxygen-rich blood to the heart. As heart cells are traumatized, the contents of mitochondria – a cell’s energy center – leak out. So begins a downward spiral that leads to cell death.

Sussman’s team studies the biochemical signals that comprise survival signaling cascades, responsible for protecting mitochondria from damage.

Funded in part by a $9.5-million grant from the National Institutes of Health, Sussman is currently exploring how the signals work. He has discovered that Pim-1, a protein induced by injury to the heart, could be the key to regenerating heart cells and enhancing their survival.

“The heart evolved to replace cells lost from everyday activity, not to replace the massive quantity of cells lost during and after a heart attack,” Sussman said.  “By using Pim-1, we can activate stem cells in the heart and regenerate heart cells.

“Our piece of the puzzle is bringing the entire field closer to the time when we will rebuild and repair the damaged heart at a molecular level to make it as healthy as it was at a younger age.”

Making the connection

Researchers have known that bone marrow continuously expresses high levels of Pim-1 throughout life, enhancing survival and proliferation of stem cells. But Sussman’s team found that Pim-1 was also expressed in the heart during neonatal development and re-expressed in response to traumatic injury.

Based on these findings, Sussman envisions a connection between Pim-1 and the survival and regeneration of heart muscle cells. In ongoing studies conducted in the Sussman lab, researchers take stem cells from the heart and engineer them through molecular biology to express Pim-1. They implant the cells into hearts injured by a coronary blockage to simulate a heart attack.

In all cases, Pim-1 has done a remarkable job of enhancing the regeneration of heart muscle cells.

To recognize his seminal work in regenerative heart research and foster Sussman’s continued accomplishments in this exciting new field, San Diego State has named him the Albert W. Johnson Research Lecturer for 2008.

Lorena Ruggero contributed to this story.