Aged, damaged hearts yield stem cells that could treat heart failure

November 17, 2010

Cardiac stem cells -- even in elderly and sick patients -- could generate new heart muscle and vessel tissue and be used to treat heart failure, according to research presented at the American Heart Association's Scientific Sessions 2010.

Scientists surgically removed tissue from the muscular wall of the heart's chambers in 21 patients. They then isolated and multiplied the cardiac stem cells (CSCs) found there. Most of the patients had ischemic cardiomyopathy (enlarged and weakened muscle due to coronary artery disease). Eleven also had diabetes. The average age of patients was about 65.

"Regardless of the gender or age of the patient, or of diabetes, we were able to isolate in all of them a pool of functional cardiac stem cells that we can potentially use to rescue the decompensated human heart," said Domenico D'Amario, M.D., Ph.D., author of the study and a postdoctoral fellow at the Center for Regenerative Medicine at Harvard, Boston, Mass.

Among the 12 female and nine male patients, researchers obtained 20 percent more CSCs from the hearts of the women than the men. Age or diabetes status didn't affect the number of cells harvested.

Women have a longer life span than men, and even with heart failure their hearts generally show more resilience -- possibly explaining the researchers' finding, D'Amario said.

The researchers also examined stem cells' biological properties that would influence their therapeutic value. They found that cells had long telomeres, or "caps," on their chromosomal ends indicating that expanded CSCs retained a significant growth reserve, although less so in older or diabetic patients.

On the same study, scientists also studied activation of a cell surface marker, insulin growth factor receptor 1 (IGF-1R), which recognizes stem cells that are most likely to thrive and have the potential to produce new cardiac tissue.

"Now you have a resident cardiac stem cell that is already programmed to form cardiac muscle, so this cell is already superior to any other cell you can take from other tissues," said Piero Anversa, M.D., senior author of the study and director of the Center for Regenerative Medicine.

CSCs are distributed throughout the cardiac muscle, but the atrial and apical regions of the heart contain niches, where the cells are protected from the physical stress of the heartbeat.

The heart's CSC reserve is present regardless of patient differences in ethnicity, background, diet and other factors. Research in more patients is needed to bolster the strength of the data, Anversa said.

Other co-authors are: Konrad Urbanek, M.D.; Toru Hosoda, M.D., Ph.D.; Hanqiao Zheng, M.D.; Annarosa Leri, M.D.; Erik Sylvin, M.D.; David D'Alessandro, M.D.; Robert E. Michler, M.D.; Jan Kajstura, Ph.D.; Filippo Crea, M.D.; Roberto Bolli, M.D.; Piero Anversa, M.D. Author disclosures are on the abstract.

The National Institutes of Health funded the study.

Contact information: Dr. D'Amario can be reached at (857) 869-8391; domenico.damario@gmail.com. (Please do not publish contact information.)

(Note: Actual presentation time is 11:30 a.m., Wed. Nov. 17, 2010)

ALSO NOTE this news tip for release at 9:30 a.m. CT, Wednesday, Nov. 17, 2010

Abstract 17367/P5088 - Aging heart can replace lost muscle cells at substantial rate, study shows

A loss of heart muscle cells that occurs with aging is compensated for in part by an increased replenishment of those cells, new research shows.

Researchers examined the hearts of 32 women and 42 men who died from causes other than cardiovascular disease for the effects of age and gender on the turnover rate of the heart muscle cells, known as cardiomyocytes. The subjects ranged in age from 19 to 104 years old.

The scientists measured the average age of cardiomyocytes, their distribution across ages, their turnover rate, and the time until the cells stop dividing. They found that the cells' renewal occurred more extensively in hearts from women than from men:The rate of programmed cell death, or apoptosis, of myocytes was higher in men than in women across the age spectrum, although the sexes didn't differ in rate of increase in cell death that occurred with age.

"The human heart is a highly dynamic organ in which myocyte loss is counteracted in part by myocyte renewal," the researchers said. "Myocyte regeneration during physiological aging takes place at previously unexpected levels in both women and men."

Jan Kajstura, Ph.D., Brigham and Women's Hospital, Boston, Mass.; (617) 525-8169; jkajstura@zeus.bwh.harvard.edu. (Please do not publish contact information.)
-end-
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.heart.org/coporatefunding.

NR10-1151 (SS10/ D'Amario and Kajstura)

Additional resources:

American Heart Association

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