The review aims to highlight recent advances in cardiac and skeletal muscle cell grafting for myocardial
Fetal and neonatal cardiomyocytes form new myocardium in normal or injured hearts, and this new
myocardium differentiates toward an adult phenotype. Unfortunately, formation of new myocardium is
limited by graft cell death, in large part because of ischemic injury. In contrast, skeletal myoblasts
are ischemia-resistant and form larger grafts of mature skeletal muscle in the injured heart. Although
contractile under field stimulation, skeletal muscle grafts do not express gap junction proteins and
remain electrically insulated, suggesting they may not beat with host myocardium. When placed in
coculture, however, cardiac and skeletal muscle form synchronously beating networks, where cardiomyocytes
capture and pace skeletal muscle cells via intercalated disk-like structures containing gap junctions.
This suggests that engineering skeletal muscle to express gap junction proteins in vivo may induce
similar coupling with host myocardium. One major challenge to myocardial repair is getting sufficient
graft cell mass without risking a tumor-like overgrowth. Recent experiments suggest it may be possible
to control skeletal muscle graft size using a small, synthetic ligand, which activates the fibroblast
growth factor signaling pathway only in genetically modified graft cells. Finally, a review of
functional studies is presented that provides clear evidence that skeletal myoblast grafting is
beneficial by limiting remodeling of the heart after infarction.
Given that clinical trials of skeletal myoblast grafting for myocardial repair are under way, it will be
critically important to determine if these cells beat after grafting in the heart.
Muscle Cell Grafting for the Treatment and Prevention of Heart Failure
Charles E. Murry, Marsha L. Whitney, Hans Reinecke
Journal of Cardiac Failure • Volume 8 • Number 6 Suppl. • Pages S532-S541 • 2002