Which skeletal myoblasts and how to be transplanted for cardiac repair?

• Published in: Biochemical and biophysical research communications Vol. 369; no. 1; pp. 270 - 276
• Main Authors: Tezuka, Asaki, Kawada, Tomie, Nakazawa, Mikio, Masui, Fujiko, Konno, Satoshi, Nitta, Shin-ichi, Toyo-oka, Teruhiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2008
• Subjects: Animals; Cardiomyopathies - pathology; Cardiomyopathies - surgery; Cell Differentiation; Cell Proliferation; Cell transplantation; Cells, Cultured; Connexin-43; Cricetinae; Dilated cardiomyopathy; Fast-twitch muscle; Fusion; Intercalated disc; Male; Muscle, Skeletal - pathology; Muscle, Skeletal - transplantation; Myoblasts - pathology; Myoblasts - transplantation; Myocytes, Cardiac - pathology; Myosin heavy chain; Regeneration - physiology; Skeletal myoblast; Slow-twitch muscle; Treatment Outcome; δ-Sarcoglycan; Myosin heavy chain; Slow-twitch muscle; Dilated cardiomyopathy; δ-Sarcoglycan; Connexin-43; Fast-twitch muscle; Intercalated disc; Fusion; Cell transplantation; Skeletal myoblast
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.11.084

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 ∼100mg 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.