Olig2-expressing Mesenchymal Stem Cells Enhance Functional Recovery after Contusive Spinal Cord Injury

Background and Objectives: Glial scarring and inflammation after spinal cord injury (SCI) interfere with neural regeneration and functional recovery due to the inhibitory microenvironment of the injured spinal cord. Stem cell transplantation can improve functional recovery in experimental models of SCI, but many obstacles to clinical application remain due to concerns regarding the effectiveness and safety of stem cell transplantation for SCI patients. In this study, we investigated the effects of transplantation of human mesenchymal stem cells (hMSCs) that were genetically modified to express Olig2 in a rat model of SCI. Methods: Bone marrow-derived hMSCs were genetically modified to express Olig2 and transplanted one week after the induction of contusive SCI in a rat model. Spinal cords were harvested 7 weeks after transplantation. Results: Transplantation of Olig2-expressing hMSCs significantly improved functional recovery in a rat model of contusive SCI model compared to the control hMSC-transplanted group. Transplantation of Olig2-expressing hMSCs also attenuated glial scar formation in spinal cord lesions. Immunohistochemical analysis showed that transplanted Olig2-expressing hMSCs were partially differentiated into Olig1-positive oligodendrocyte-like cells in spinal cords. Furthermore, NF-M-positive axons were more abundant in the Olig2-expressing hMSC-transplanted group than in the control hMSC-transplanted group. Conclusions: We suggest that Olig2-expressing hMSCs are a safe and optimal cell source for treating SCI.ope