Comparisons of neurotrophic effects of mesenchymal stem cells derived from adipose tissue, bone marrow, and cranial bone on chronic spinal cord injury

Abstract Background Cell-based therapies with mesenchymal stem cells (MSCs) are considered as promising strategies for spinal cord injury (SCI). MSCs have unique characteristics due to difference in the derived tissues. However, relatively few studies have focused on differences in the therapeutic effects of MSCs derived from different tissues. Here, the therapeutic effects of adipose tissue-derived MSCs (aMSCs), bone marrow-derived MSCs (bMSCs), and cranial bone-derived MSCs (cMSCs) on chronic SCI model rats were compared. Methods MSCs were established from adipose tissue, bone marrow, and cranial bone collected. Neurotrophic factor expression of each MSC type was analyzed by real-time PCR. SCI rats were established with the weight-drop method and transplanted intravenously with MSCs at 4 weeks after SCI. Hind-limb motor function was evaluated from before injury to 4 weeks after transplantation. Endogenous neurotrophic factor and neural repair factor expression in spinal cord (SC) tissue were examined by real-time PCR and western blot analyses. Furthermore, the neurotrophic effects (i.e., neurite formation and elongation) of each MSC type were verified by co-culture with NG108-15 neural cells. Results Although there were no differences in the expression levels of cell surface markers and multipotency, expression of Bdnf, Ngf, and Sort1 (Nt-3) was relatively higher in cMSCs. Transplantation of cMSCs improved motor function of chronic SCI model rats. Although there was no difference in the degree of engraftment of transplanted cells in the injured SC tissue, transplantation of cMSCs enhanced Bdnf, TrkB, and Gap-43 mRNA expression and synaptophysin protein expression in injured SC tissue. In vitro, cMSCs co-cultured with NG108-15 cells promoted neurite formation and elongation. Conclusion As compared with MSCs derived other tissues, cMSCs highly express many neurotrophic factors which improved motor function in chronic SCI model rats by promoting endogenous neurotrophic and neural plasticity factors. These results suggest the efficacy of cMSCs in cell-based therapy for chronic SCI.