Skeletal myoblast transplantation for repair of myocardial necrosis.
Myocardial infarcts heal by scarring because myocardium cannot regenerate. To determine if skeletal myoblasts could establish new contractile tissue, hearts of adult inbred rats were injured by freeze-thaw, and 3-4.5 x 10(6) neonatal skeletal muscle cells were transplanted immediately thereafter. At 1 d the graft cells were proliferating and did not express myosin heavy chain (MHC). By 3 d, multinucleated myotubes were present which expressed both embryonic and fast fiber MHCs. At 2 wk, electron microscopy demonstrated possible satellite stem cells. By 7 wk the grafts began expressing beta-MHC, a hallmark of the slow fiber phenotype; coexpression of embryonic, fast, and beta-MHC continued through 3 mo. Transplanting myoblasts 1 wk after injury yielded comparable results, except that grafts expressed beta-MHC sooner (by 2 wk). Grafts never expressed cardiac-specific MHC-alpha. Wounds containing 2-wk-old myoblast grafts contracted when stimulated ex vivo, and high frequency stimulation induced tetanus. Furthermore, the grafts could perform a cardiac-like duty cycle, alternating tetanus and relaxation, for at least 6 min. Thus, skeletal myoblasts can establish new muscle tissue when grafted into injured hearts, and this muscle can contract when stimulated electrically. Because the grafts convert to fatigue-resistant, slow twitch fibers, this new muscle may be suited to a cardiac work load.
Murry
C E
CE
Department of Pathology, University of Washington School of Medicine, Seattle 98195, USA. murry@u.washington.edu
Wiseman
R W
RW
Schwartz
S M
SM
Hauschka
S D
SD
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000502:physiology* / Q000637:transplantation* / Q000648:ultrastructure; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D012518:Sarcomeres / Q000502:physiology; D016042:Transplantation, Heterotopic
D018995:Myosin Heavy Chains