Male cells in transplanted female hearts show regeneration possible

American Heart Association
Tuesday, 28 May 2002

The human heart has the potential to regenerate itself by recruiting cells from other areas of the body and putting them to work in the heart, according to an historic finding reported in the May 28th rapid track publication of Circulation: Journal of the American Heart Association. Rapid track articles are released online early because they have major clinical impact or represent important basic science discoveries.

A team of German researchers discovered the regeneration ability by examining biopsy specimens taken from men who received heart transplants from female donors. Heart muscle cells (myocytes) from male hearts were found in biopsied specimens from eight of 13 recipients of female hearts.

"The female heart was able to recruit male cells and transform them into myocytes," explains senior author Michael Böhm, M.D., professor of medicine, University of Saarlandes, Homburg, Germany. "And these male cells were not simply isolated in the tissue. They had formed intercellular connections with the female cells and were therefore probably electrically coupled and functioning with other heart muscle cells."

For years heart researchers believed that humans were born with a limited lifetime supply of myocytes - the muscle cells that work together to make the heart beat. As one ages these cells die off and are not replaced.

"Most healthy adults end up with about 50 percent of the myocytes with which they were born," says Böhm. "While a 50-percent level can keep a heart healthy, when a heart attack or chronic heart disease develops, more myocytes are killed, which can lead to heart failure."

Animal experiments suggested that it might be possible to replace myocytes with pluripotent stem cells, which are special cells that researchers believe can be transformed into a variety of cell types such as muscle or bone cells and even cardiac muscle. But this had not been proven in humans.

Mismatched gender heart transplants proved an excellent way to determine if this recruitment and regeneration actually occurs in humans. A man who has received a female heart would be expected to have only female or "X" chromosome myocytes. The presence of male or "Y" chromosome myocytes indicates both recruitment and regeneration, Böhm says.

Böhm and his colleagues examined 21 biopsy specimens taken from 13 men who received female hearts and later experienced some organ rejection. Tissues from one nontransplanted male and myocardial biopsies from sex-matched heart transplanted patients were used as controls.

While Böhm notes that this study is very preliminary, he says it opens the door for several new possibilities for improving the pump function of damaged hearts. One possibility is that stem cells could be directly transplanted into the heart where they could transform into the needed muscle cells.

Even more intriguing, he says, is research to "determine what causes the stem cells to directly invade the heart and what attracts them to differentiate into myocytes. Finding a way to recruit these cells and stimulate differentiation is an obvious next step for research."

That could be an alternative to transplanting fetal cardiomyocytes or stem cells. However, since the percentage of regenerated cardiomyocytes found in the study was low (0.16 percent), further research is needed to determine whether it is possible to regenerate enough new heart cells to significantly repair a damaged heart.

Although this new research "challenges the accepted dogma that the heart does not regenerate," Böhm predicts it will only be five to 10 years before myocyte regeneration could lead to clinical treatment for heart disease.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org