Immunosuppression of Allogenic Mesenchymal Stem Cells Transplantation after Spinal Cord Injury Improves Graft Survival and Beneficial Outcomes

Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Mesenchymal stem cells (MSC) have demonstrated beneficial effects following transplantation in animal models of SCI. However, despite the immunoprivilege properties of the MSC, their survival in the injured spinal cord is reduced due to the detrimental milieu in the damaged tissue and immune rejection of the cells. The limited survival of the engrafted cells may determine the therapy success. Therefore, we compared two strategies to increase the presence of the cells in the injured spinal cord in rats: increasing the amount of MSC transplants and using immunosuppressive treatment with FK506 after transplantation. Functional outcomes for locomotion and electrophysiological responses were assessed. The grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that immunosuppression improved grafted cells survival. A cell-dose effect was found regarding locomotion recovery and tissue protection independent of immunosuppression. Nevertheless, immunosuppression enhanced the electrophysiological outcomes and allowed filling of the cavity formed after injury by new regenerative tissue and axons. These results indicate that MSC transplantation combined with immunosuppression prolongs the survival of engrafted cells and improves functional and morphological outcomes after SCI.