DIFFERENTIATION AND LONG-TERM SURVIVAL OF C2C12 MYOBLAST GRAFTS IN HEART

We have assessed the ability of skeletal myoblasts to form long-term, differentiated grafts in ventricular myocardium. C2C12 myoblasts were grafted directly into the heart of syngeneic mice. Viable grafts were observed as long as 3 mo after implantation. Immunohistological analys es revealed the presence of differentiated myotubes that stably expres sed the skeletal myosin heavy chain isoform. Thymidine uptake studies indicated that virtually all of the grafted skeletal myocytes were wit hdrawn from the cell cycle by 14 d after grafting. Graft myocytes exhi bited ultrastructural characteristics typical of differentiated myotub es. Graft formation and the associated myocardial remodeling did not i nduce overt cardiac arrhythmia. This study indicates that the myocardi um can serve as a stable platform for skeletal myoblast grafts. The lo ng-term survival, differentiated phenotype, and absence of sustained p roliferative activity observed in myoblast grafts raise the possibilit y that similar grafting approaches may be used to replace diseased myo cardium. Furthermore, the genetic tractability of myoblasts could prov ide a useful means for the local delivery of recombinant molecules to the heart.