1,25-Dihydroxyvitamin D₃Increases 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-D 3 (1,25-D 3 ) acted directly on myoblasts, regulating their proliferation and fusion. 1,25-D 3 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-D 3 could improve the hMPC graft success. The 1,25-D 3 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-D 3 to determine its in vivo effect. Graft success, proliferation, and viability of transplanted hMPCs were evaluated. 1,25-D 3 enhanced proliferation and fusion of hMPCs in vitro and in vivo. However, 1,25-D 3 did not protect hMPCs from various proapoptotic factors (in vitro) or during the early posttransplantation period. 1,25-D 3 enhanced hMPC graft success because the number of muscle fibers expressing human dystrophin was significantly increased in the TA sections of 1,25-D 3 -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-D 3 . Thus, 1,25-D 3 administration could improve the clinical potential of hMPC transplantation currently developed for muscle trauma or myopathies.

1α,25(OH)2-Vitamin D3 Increases Dysferlin Expression in vitro and in a Human Clinical Trial

“…32 Also, it has been reported that D3 enhances grafting of human muscle precursor cells (hMPCs) into muscle after transplantation into SCID mice. 33 The authors suggested that D3 increase proliferation and differentiation of hMPCs and that this would explain the transplantation improvement. Our present results suggest that the improvement could be due to an increase of dysferlin expression after treatment of hMPCs with D3.…”

Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice

“…Its success relies on the incorporation of these cells into regenerating myofibers. Progenitor cells derived from both skeletal muscle (34,49,55,57) as well as from other tissues (1,13, 21,52,59) have been explored for this purpose (6,44,47). Although experimental and clinical studies with myoblasts have yielded important insights, their clinical application is hampered by (i) limited availability, (ii) restricted ex vivo proliferation capacity, and (iii) limited spread in host muscles (45,56,60).…”