CELLULAR CARDIOMYOPLASTY - MYOCARDIAL REGENERATION WITH SATELLITE CELL IMPLANTATION

Background. Damaged skeletal muscle is able to regenerate because of t he presence of satellite cells, which are undifferentiated myoblasts. In contrast, destruction of cardiac myocytes is associated with an irr eversible loss of myocardium and replacement with scar tissue, because it lacks stem cells. We tested the hypothesis that skeletal muscle sa tellite cells implanted into injured myocardium can differentiate into cardiac muscle fibers and thus repair damaged heart muscle. Methods. Two series of canine studies were performed. In the first series (n = 26), satellite cells were isolated from skeletal muscle, cultured, and labeled with tritiated thymidine. The cells were implanted into acute ly cryoinjured myocardium and the specimens harvested 4 to 18 weeks la ter. In the second series (n = 20), satellite cells in culture were la beled with lacZ reporter gene, which encodes production of Escherichia coli beta-galactosidase. Four to 6 weeks later, beta-galactosidase ac tivity was studied using X-Gal stain. Results. New striated muscles we re found in the first series of experiments at the site of implantatio n, within a dense scar created by cryoinjury. These muscles showed his tologic evidence of intercalated discs and centrally located nuclei, s imilar to those seen in cardiac muscle fibers. Tritiated thymidine rad ioactivity was not identified clearly, presumably due to dilutional ef fect as the stem cells replicated repeatedly. In the second series, hi stochemical studies of reporter gene-labeled and implanted satellite c ells revealed the presence of beta-galactosidase within the cells at t he implant site, which confirmed the survival of implanted cells. Conc lusions. Our data are consistent with the hypothesis of milieu-influen ced differentiation of satellite cells into cardiac-like muscle cells. Confirmation of these findings and its functional capabilities could have important clinical implications.