1,25-Dihydroxyvitamin D 3 Increases the Transplantation Success of Human Muscle Precursor Cells in SCID Mice

Abstract

Human muscle precursor cell (hMPC) transplantation is a potential therapy for severe muscle trauma or myopathies. Some previous studies demonstrated that 1,25-dihydroxyvitamin-D₃ (1,25-D₃) acted directly on myoblasts, regulating their proliferation and fusion. 1,25-D₃ is also involved in apoptosis modulation of other cell types and may thus contribute to protect the transplanted hMPCs. We have therefore investigated whether 1,25-D₃ could improve the hMPC graft success. The 1,25-D₃ effects on hMPC proliferation, fusion, and survival were initially monitored in vitro. hMPCs were also grafted in the tibialis anterior of SCID mice treated or not with 1,25-D₃ to determine its in vivo effect. Graft success, proliferation, and viability of transplanted hMPCs were evaluated. 1,25-D₃ enhanced proliferation and fusion of hMPCs in vitro and in vivo. However, 1,25-D₃ did not protect hMPCs from various proapoptotic factors (in vitro) or during the early posttransplantation period. 1,25-D₃ enhanced hMPC graft success because the number of muscle fibers expressing human dystrophin was significantly increased in the TA sections of 1,25-D₃-treated mice (166.75 ± 20.64) compared to the control mice (97.5 ± 16.58). This result could be partly attributed to the improvement of the proliferation and differentiation of hMPCs in the presence of 1,25-D₃. Thus, 1,25-D₃ administration could improve the clinical potential of hMPC transplantation currently developed for muscle trauma or myopathies.