Evaluation of the survival of bone marrow-derived mononuclear cells and the growth factors produced upon intramedullary transplantation in rat models of acute spinal cord injury. (August 2016) - Arai, Kiyotaka
Abstract: Intramedullary bone marrow-derived mononuclear cell (BM-MNC) transplantation has demonstrated neuroprotective effects in the chronic stage of spinal cord injury (SCI). However, no previous study has evaluated its effects in the acute stage, even though cell death occurs mainly within 1 week after injury in all neuronal cells. Moreover, the mechanism underlying these effects remains unclear. We aimed to investigate the survival of intramedullary transplanted allogeneic BM-MNCs and the production of growth factors after transplantation to clarify the therapeutic potential of intramedullary transplanted BM-MNCs and their protective effects in acute SCI. Sprague-Dawley rats were subjected to traumatic SCI and received intramedullary transplantation of EGFP + BM-MNCs (n = 6), BM-MNCs (n = 10), or solvent (n = 10) immediately after injury. To evaluate the transplanted BM-MNCs and their therapeutic effects, immunohistochemical evaluations were performed at 3 and 7 days post-injury (DPI). BM-MNCs were observed at the injected site at both 3 (683 ± 83 cells/mm 2 ) and 7 DPI (395 ± 64 cells/mm 2 ). The expression of hepatocyte growth factor was observed in approximately 20% transplanted BM-MNCs. Some BM-MNCs also expressed monocyte chemotactic protein-1 or vascular endothelial growth factor. The demyelinated area and number of cleaved caspase-3-positive cells were significantly smaller in the BM-MNC-transplanted group at 3 DPI. Hindlimb locomotor function was significantly improved in the BM-MNC-transplanted group at 7 DPI. These results suggest that intramedullary transplantation of BM-MNCs is an efficient method for introducing a large number of growth factor-producing cells that can induce neuroprotective effects in the acute stage of SCI. Graphical abstract: Highlights: Transplanted BM-MNCs survived in the spinal cord lesion for 7 days. Subpopulation of the BM-MNCs produced HGF, VEGF, and MCP-1 in the spinal cord lesion. Intramedullary BM-MNCs transplantation reduced the apoptotic cells in acute SCI. Intramedullary BM-MNCs transplantation suppressed demyelination in acute SCI.