蛛网膜下腔移植人脐带间充质干细胞修复大鼠脊髓损伤

Transplantation of human umbilical cord derived-mesenchymal stem cells via subarachnoid space way for the treatment of spinal cord injury in rats

目的 观察蛛网膜下腔途径移植人脐带间充质干细胞（hUC-MSCs）修复大鼠脊髓损伤的疗效.方法 雌性Wistar大鼠40只建立脊髓损伤模型后随机分为：空白对照组（A组）、蛛网膜下腔DMEM注射组（B组）和hUC-MSCs移植组（C组）.通过行为学及电生理学评价损伤大鼠后肢功能恢复情况.免疫荧光染色观察hUC-MSCs存活、迁移、分化,胶质酸性蛋白（GFAP）染色比较各组损伤局部胶质瘢痕面积差异.结果 移植4周后BBB评分,C组（9.19±0.26）高于A组（8.19±0.46）、B组（8.31±0.37）,差异有统计学意义（P＜0.05）.损伤后12周C组体感诱发电位（SEP）、运动诱发电位（MEP）潜伏期缩短和波幅值增高与其他组比较差异有统计学意义（P＜0.05）.hUC-MSCs到达损伤局部并向神经元、星形胶质细胞和少突胶质细胞分化,分化的少突胶质细胞包绕轴突形成髓鞘.损伤局部胶质瘢痕面积C组（40 261.93±9137.56）均小于A组（203127.88±16448.84）、B组（219 622.47±18 944.89）,差异有统计学意义（P＜0.05）,A、B组间差异无统计学意义（P＞0.05）.结论 hUC-MSCs可经蛛网膜下腔途径到达损伤局部并促进大鼠脊髓损伤的功能恢复.

Objective To evaluate the repair ability of transplanting human umbilical cord derived-mesenchymal stem cells （hUC-MSCs） into spinal cord-injured rats via subarachnoid space way.Methods Forty female Wistar rats which subjected to spinal cord injury were assigned into three groups randomly： plain control group （group A）, subarachnoid space way transplanted DMEM group （group B）and transplanted hUC-MSCs group （group C）. The recoveries of the lower extremity were observed by Basso-Beattie-Bresnahan （BBB） locomotor scoring system, somatosensory evoked potential （SEP） and motor evoked potentials （MEP）. Also, migration, differentiation and survival of hUC-MSCs in the injured site were observed by immunohistochemistry. The area of glial scar in the injured site was calculated by immunostaining against GFAP. Results BBB score in group C （9. 19 ± 0. 26） was significantly higher than in groups A （8. 19 ± 0. 46） and B （ 8. 31 ± 0. 37 ） 4 weeks after injury （P 〈 0. 05 ）. For SEP and MEP, latency period was shortened and wave amplitude was increased in group C as compared with groups A and B （ P 〈 0. 05）. Immunohistochemical staining revealed that hUC-MSCs could reached the injured site and differentiated into neuronal cells, oligodendrocytes and astrocytes. The area of glial scar in group C （40 261.93 ±9137. 56） was smaller than in group A （20 3127. 88 ± 16 448. 84） and B （219 622. 47 ± 18944. 89,P 〈0. 05）. Conclusion HUC-MSCs transplanted through subarachnoid space could migrate to the injured parenchyma of spinal cord and repair spinal cord injury effectively.