Combination of bone marrow stromal cell transplantation with mobilization by granulocyte-colony stimulating factor promotes functional recovery after spinal cord transection.

Abstract

Spinal cord injury (SCI) results in severe neurological deficit. However, the functional recovery following SCI is very poor due to the neural lost and limited axonal regeneration. To date, there was no effective treatment. Recent studies have shown that bone marrow stromal cells (BMSCs) transplantated into the central nervous system (CNS) can survive and differentiate into neuronal-like cells. Additionally, granulocyte colony-stimulating factor (G-CSF) can mobilize hematopoietic stem cells and inhibit neural cell apoptosis. Thus, we aimed to evaluate the combined effect of BMSC transplantation and G-CSF administration on rats with traverse spinal cord injury. BMSCs were cultured in vitro, labeled with Hoechst33342, and then transplanted into the lesion site with or without G-CSF administration (50 microg/kg/day) for 5 subsequent days. The groups included an untreated control, along with treatment by G-CSF alone, BMSCs alone, and G-CSF + BMSCs. In this study, by the end of eighth week after SCI injury, the animals in group treated with G-CSF + BMSCs showed higher BBB scores than the other two groups. Morphometric assessment showed that the lesion areas in the rats of the G-CSF + BMSCs group were much smaller. Compared with the control, BMSC, and G-CSF groups, less expression of apoptosis cells and more neural-cell markers around the spinal cord injury were found in rats treated with G-CSF + BMSCs. The animals with the combination treatment achieved a better functional and morphologic recovery, although partial. This synergistic effect between BMSCs and G-CSF may be attributed to extrinsic and endogenous neurogenesis in the traverse spinal cord injury.