Co-transplantation of bone mesenchymal stem cells with chondroitin sulfate enzymes through different routes in treating spinal injuries in rabbits

Abstract

Objective To compare the effects of different treatment routes on spinal cord injuries (SCI) in rabbits by co-transplantation of bone mesenchymal stem cells (BMSCs) with chondroitin sulfate enzymes (ChABC).Methods Twenty-four SCI rabbits were randomized into injury control group (IC),intraspinal treatment group (IS),intravenous treatment group (IV) and intraarterial treatment group (IA,n=6); BMSCs combined with ChABC were transplanted to the spinal cord tissue through the above three routes one week after SCI,respectively.Animal behavior evaluation,neural electrophysiology examination,and fluorescence tracer and immunohistochemical methods were used to compare with curative effects of co-transplantation via different routes in rabbit spinal cord injuries before SCI,and 1,2,3 and 4 weeks after SCI.Results Modified Tarlov scale scores:three weeks after SCI,Tarlov scale scores in IA group significantly increased as compared with that of IC group (P＜0.05); four weeks after SCI,three treatment groups recovered more significantly than IC group (P＜0.05).Hematoxylin-Eosin (HE) staining showed that large vacuoles were found at the spinal cord tissues of the IC group,while smaller vacuoles and visible part of the nerve fibers passing through were noted at the three treatment groups.Immunohistochemical method indicated that the expression of neurofilament 200 (NF200) was obviously more intense and that of glial fibrillary acidic portein (GFAP) was significantly weaker in the three treatment groups as compared with those in IC group (P＜0.05); IS group and IA group had more intense NF200 expression than that in IV group (P＜0.05); for GFAP expression,the highest expression was found in IC group,while that expression in IS and IA group was weaker and group IV was much obvious,with significant differences (P＜0.05).Double staining comparison:four weeks after SCI,many PKH-DAPI positive cells were seen in the three treatment groups under high magnification,and the migration ratios of the IS and IA group were higher than those of IV group,with statistically significant differences (P＜0.05).Latency period and wave amplitude in somatosensory evoked potential:third and fourth week after injury,the latency period and wave amplitude of the three treatment groups recovered better than those ofIC group with significant differences (P＜0.05); four weeks after SCI,IS group and IA group recovered better than IV group with statistically significant differences (P＜0.05).Conclusions The above three transplantation routes achieve good curative effect.Delivery though IS and IA routes are more effective than IV route. Key words: Spinal cord injury; Bone mesenchymal stem cell; Chondroitin sulfate enzyme; Transplantation route