Stem Cells and the Regenerating Heart

The impediment to adult mammalian cardiac regeneration has been attributed to its distinct embryonic history, and to the relative paucity of progenitor cells residing within the heart. The primitive heart tube, composed of contracting cardiomyocytes lined by a layer of endocardial cells, ensures the establishment of a circulatory system which is critical to support rapid rates of embryonic growth. Actively contracting fetal cardiomyocytes must continue to divide to provide for further growth of the embryonic heart. A recent report shows that the heart possesses regenerating capacities in which stem or precursor cells "refresh" adult mammalian cardiomyocytes after ischemia or pressure overload, but not during aging. Strategies have been proposed to regenerate the heart via cell therapy, combined with tempering the hostile environment of the infarct, by administration of cell survival and antiinflammatory molecules. Important advances in the control of stem cell fate have also moved the field of regenerative medicine closer towards applicable therapies for cardiac muscle regeneration. The field has yet to overcome significant obstacles, including the incomplete cell differentiation of stem cells, the paucity of organ-specific stem cell resources, and the immunogenicity of the transplanted cells. The presence of a circulating cell population that could restore the heart has gained credibility from observations of sex-mismatched cardiac human transplants in which a female heart is transplanted into a male host. Emerging concepts of regeneration as an evolutionary variable are dramatically illustrated by the relatively robust proliferative capacity of the injured heart in other vertebrate species.