Which skeletal myoblasts and how to be transplanted for cardiac repair?
Clinical efficacy of skeletal myoblast (skMb) transplantation is controversial whether this treatment produces beneficial outcome in patients with dilated cardiomyopathy (DCM). Based on immunological tolerance between wild-type and DCM hamsters with the deletion of delta-sarcoglycan (SG) gene, skMb engraftment in TO-2 myocardium (3x10(5) cells in approximately 100mg heart) was verified by the donor-specific expression of delta-SG transgene constitutively produced throughout myogenesis. At 5 weeks after the transplantation, the cell rates expressing fast-myosin heavy chain (MHC) exceeded slow-MHC in delta-SG(+) cells. Fifteen weeks after (corresponding to approximately 12 years in humans), fast MHC(+) cells nullified, but the delta-SG(+) and slow MHC(+) cell number remained unaltered. These skMbs fused with host cardiomyocytes via connexin-43 and intercalated disc, modestly improving the hemodynamics without arrhythmia, when engrafted skMbs were sparsely disseminated in autopsied myocardium. These results provide us evidence that disseminating delivery of slow-MHC(+) myoblasts is promising for repairing DCM heart using histocompatible skeletal myoblasts in future.
Department of Pathophysiology and Internal Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Asaki
A
Tezuka
Tomie
T
Kawada
Mikio
M
Nakazawa
Fujiko
F
Masui
Satoshi
S
Konno
Shin-Ichi
S
Nitta
Teruhiko
T
Toyo-Oka
D000818:Animals; D009202:Cardiomyopathies / Q000473:pathology* / Q000601:surgery*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006224:Cricetinae; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology* / Q000637:transplantation*; D032446:Myoblasts / Q000473:pathology* / Q000637:transplantation*; D032383:Myocytes, Cardiac / Q000473:pathology*; D012038:Regeneration / Q000502:physiology; D016896:Treatment Outcome