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 δ-sarcoglycan (SG) gene, skMb engraftment in TO-2 myocardium (3 × 105 cells in ∼100 mg heart) was verified by the donor-specific expression of δ-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 δ-SG+ cells. Fifteen weeks after (corresponding to ∼12 years in humans), fast MHC+ cells nullified, but the δ-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.