Rcj. Chiu et al., CELLULAR CARDIOMYOPLASTY - MYOCARDIAL REGENERATION WITH SATELLITE CELL IMPLANTATION, The Annals of thoracic surgery, 60(1), 1995, pp. 12-18
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.