title: Skeletal myoblast transplantation for repair of myocardial necrosis.
abstract: 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.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle 98195, USA. murry@u.washington.edu
authors.forename: C E
authors.initials: CE
authors.lastname: Murry
authors.forename: R W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: S M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: S D
authors.initials: SD
authors.lastname: Hauschka
mesh_terms: 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
chemical_list: D018995:Myosin Heavy Chains