1,25-dihydroxyvitamin D3 increases the transplantation success of human muscle precursor cells in SCID mice.
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.
Unité de Génétique Humaine, Centre de Recherche du CHUL, Université Laval, Québec, Canada.
Lionel
L
Stephan
Manaf
M
Bouchentouf
Philippe
P
Mills
Jean-François
JF
Lafreniere
Jacques P
JP
Tremblay
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016189:Dystrophin / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D006801:Humans; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D016513:Mice, SCID; D032342:Muscle Cells / Q000637:transplantation*; D015996:Survival Rate; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000627:therapeutic use
D016189:Dystrophin; C118756:dihydroxy-vitamin D3; D014807:Vitamin D