Columbia Researchers Repair Heart Damage In Mice By Activating Gene To Make Adult Heart Stem Cells Regenerate

NEW YORK - Adult heart cells usually lack the ability to regenerate, preventing the heart from repairing itself after a heart attack. But in a recent study, Columbia researchers have successfully turned on a gene in adult mice that makes stem cells in the heart divide and allows them to repair potentially deadly heart damage.

Hina Chaudhry, MD The gene, known as cyclin A2, is active at the embryonic stage, but is turned off in all adult mammals. The researchers were able to activate the cyclin A2 gene in adult mice by genetically altering mice so that the gene remained active in adults. These mice were able to repair their hearts after heart attacks, unlike normal mice.

The research is published in the June, 2007 issue of Circulation Research, a publication of the American Heart Association.

“This gene is a critically important regulator of cell division, and this study brings us much closer to understanding how to activate it to generate cells to repair heart damage in humans,” said Hina Chaudhry, MD, assistant professor of medicine at Columbia University Medical Center and the principal investigator of the study.

Previously published reports have shown that hearts are unable to repair damage caused by heart attacks because the cyclin A2 gene has been shut off, preventing cells from dividing and multiplying into new healthy cells. Over time, the scarring becomes worse and pulls on healthy regions of the heart, causing the ventricle to dilate or become closed off. This makes the heart’s pumping function decrease, causing blood to back up into the lungs, arrhythmias, and other potentially fatal complications.

This process, known as heart failure, is the leading cause of hospitalization in people older than 65. Nearly five million Americans are affected by heart failure, and roughly 550,000 people are diagnosed with heart failure each year.

In the mouse study, the researchers were able to illustrate that the cyclin A2 gene regenerates the heart, rather than preventing damage from occurring in the first place. The mice with the activated gene and another group without the activation both suffered from heart damage a week after having a heart attack. But three months after the heart attacks, the mice with the activated cyclin A2 gene had 77 percent better heart function than the other mice.

Dr. Chaudhry said the potential applications for cardiac repair in humans could include activating the gene in human hearts to stimulate regeneration, or growing cardiac stem cells outside the body for therapeutic implantation into the heart. ### Columbia University Medical Center provides international leadership in pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. www.cumc.columbia.edu

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Circulation Research, Dental Medicine, Hina Chaudhry, Mailman School, Physicians Surgeons