BACKGROUND AND PURPOSE: Studies have shown that the administration of Taxol, an anti-cancer drug, inhibited scar formation, promoted axonal elongation and improved locomotor recovery in rats after spinal cord injury (SCI). We hypothesized that combining Taxol with another promising therapy, transplantation of human umbilical mesenchymal stem cells (hUCMSCs), might further improve the degree of locomotor recovery. The present study examined whether Taxol combined with transplantation of hUCMSCs would produce synergistic effects on recovery and which mechanisms were involved in the effect. METHODS: A total of 32 rats subjected to SCI procedures were assigned to one of the following four treatment groups: phosphate-buffered saline (PBS, control), hUCMSCs, Taxol, or Taxol+hUCMSCs. Immediately after injury, hUCMSCs were transplanted into the injury site and Taxol was administered intrathecally for 4 weeks. Locomotor recovery was evaluated using the Basso, Beattie and Bresnahan locomotor (BBB) rating scale. Survival of the transplanted human cells and the host glial reaction in the injured spinal cord were studied by immunohistochemistry. RESULTS: Treatment with Taxol, hUCMSCs or Taxol+hUCMSCs reduced the extent of astrocytic activation, increased axonal preservation and decreased the number of caspase-3(+) and ED-1(+) cells, but these effects were more pronounced in the Taxol+hUCMSCs group. Behavioral analyses showed that rats in the Taxol+hUCMSCs group showed better motor performance than rats treated with hUCMSCs or Taxol only. CONCLUSIONS: The combination of Taxol and hUCMSCs produced beneficial effects in rats with regard to functional recovery following SCI through the enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal preservation effects.
BACKGROUND AND PURPOSE: Studies have shown that the administration of Taxol, an anti-cancer drug, inhibited scar formation, promoted axonal elongation and improved locomotor recovery in rats after spinal cord injury (SCI). We hypothesized that combining Taxol with another promising therapy, transplantation of human umbilical mesenchymal stem cells (hUCMSCs), might further improve the degree of locomotor recovery. The present study examined whether Taxol combined with transplantation of hUCMSCs would produce synergistic effects on recovery and which mechanisms were involved in the effect. METHODS: A total of 32 rats subjected to SCI procedures were assigned to one of the following four treatment groups: phosphate-buffered saline (PBS, control), hUCMSCs, Taxol, or Taxol+hUCMSCs. Immediately after injury, hUCMSCs were transplanted into the injury site and Taxol was administered intrathecally for 4 weeks. Locomotor recovery was evaluated using the Basso, Beattie and Bresnahan locomotor (BBB) rating scale. Survival of the transplanted human cells and the host glial reaction in the injured spinal cord were studied by immunohistochemistry. RESULTS: Treatment with Taxol, hUCMSCs or Taxol+hUCMSCs reduced the extent of astrocytic activation, increased axonal preservation and decreased the number of caspase-3(+) and ED-1(+) cells, but these effects were more pronounced in the Taxol+hUCMSCs group. Behavioral analyses showed that rats in the Taxol+hUCMSCs group showed better motor performance than rats treated with hUCMSCs or Taxol only. CONCLUSIONS: The combination of Taxol and hUCMSCs produced beneficial effects in rats with regard to functional recovery following SCI through the enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal preservation effects.
Authors: Patrick M Kochanek; Travis C Jackson; Nikki Miller Ferguson; Shaun W Carlson; Dennis W Simon; Erik C Brockman; Jing Ji; Hülya Bayır; Samuel M Poloyac; Amy K Wagner; Anthony E Kline; Philip E Empey; Robert S B Clark; Edwin K Jackson; C Edward Dixon Journal: Semin Neurol Date: 2015-02-25 Impact factor: 3.420