Hypoxic preconditioned bone mesenchymal stem cells ameliorate spinal cord injury in rats via improved survival and migration

The unique hypoxic inflammatory microenvironment observed in the spinal cord following spinal cord injury (SCI) limits the survival and efficacy of transplanted bone mesenchymal stem cells (BMSCs). The aim of the present study was to determine whether hypoxic preconditioning (HP) increased the therapeutic effects of BMSC on SCI. BMSCs were pretreated with cobalt chloride (CoCl(2)) in vitro, and the proliferative apoptotic and migratory abilities of these hypoxic BMSCs (H-BMSCs) were assessed. BMSCs and H-BMSCs derived from green fluorescent protein (GFP) rats were transplanted into SCI rats in vivo. The neurological function, histopathology, inflammation, and number and migration of transplanted cells were examined. HP significantly enhanced BMSC migration (increased hypoxia inducible factor 1α and C-X-C motif chemokine receptor 4 expression) and tolerance to apoptotic conditions (decreased caspase-3 and increased B-cell lymphoma 2 expression) in vitro. In vivo, H-BMSC transplantation significantly improved neurological function, decreased spinal cord damage and suppressed the inflammatory response associated with microglial activation. The number of GFP-positive cells in the SCI core and peripheral region of H-BMSC animals was increased compared with that in those of BMSC animals, suggesting that HP may increase the survival and migratory abilities of BMSCs and highlights their therapeutic potential for SCI.