脂肪来源干细胞移植对脑缺血大鼠运动功能的影响

目的 观察脂肪来源干细胞(ADAS)移植入脑缺血大鼠后存活、迁移、分化以及大鼠的运动功能障碍恢复情况,探讨ADAS移植治疗大鼠局灶性脑缺血的有效性和可能机制. 方法 将雄性SD大鼠饲养至250～300 g时,制作左侧大脑中动脉阻塞模型(MCAO),按照随机数字表法分为未处理组、对照组和移植组,每组6只.未处理组造模后不作特殊处理,对照组在造模后3h通过尾静脉注射杜氏改良培养基(DMEM),移植组造模后3 h通过尾静脉注射ADAS.造模后14 d处死大鼠,通过免疫荧光染色观察5-溴脱氧尿嘧啶核苷(BrdU)、神经元特异性烯醇化酶(NSE)、人微管相关蛋白2(MAP-2)和神经胶质纤维酸性蛋白(GFAP)的表达.造模后1、7及14 d时神经功能缺损评分评价大鼠运动功能改善情况. 结果 (1)移植后,标记了BrdU的ADAS大量出现在缺血灶周围;(2)MCAO后14d,缺血灶周围出现了少量BrdU/GFAP双染阳性细胞;同时出现少量BrdU/NSE和BrdU/MAP-2双染阳性细胞;(3)14d时移植组大鼠神经功能缺损评分与对照组相比明显降低,差异有统计学意义(P＜0.05). 结论 (1)成年大鼠ADAS在MCAO大鼠体内存活并少量分化为神经元样细胞和星形胶质细胞样细胞;(2)移植ADAS可使大鼠脑缺血所致的运动功能缺损得到改善.

Adipose-derived stem cell transplantation on motor function of ischemic rats

Objective To observe the survival, migration and differentiation of adipose-derived adult stem (ADAS) cells and the recovery of motor function of ischemic rats after ADAS cell transplantation. Methods Eighteen adult male SD rats, weighted about 250-300 g, were chosen and received left middle cerebral artery occlusion (MCAO) operation. And then, they were equally randomized into untreated group, control group and ADAS cell transplantation group. Tail vein injection of Dulbecco's modified eagles medium (DMEM) and ADAS cells were performed in the control group and ADAS cell transplantation group 3 h after MCAO, respectively. These animals were euthanized 14 d after MCAO. Immunofluorescence for BrdU, NSE, MAP-2 and GFAP were processed to identify the survival, migration and differentiation of grafted ADAS cells in the brain, and at the same time, scores of neurological deficit scale were used to assess the improvement of motor function. Results After the transplantation, numerous ADAS cells labeled with BrdU were presented in the ischemic points and surrounding areas. A few BrdU/GFAP, BrdU/NSE and BrdU/MAP-2 -positive cells were noted in the ischemic points of ADAS transplantation group 14 d after MCAO. The neurological functional recovery in the ADAS cell transplantation group was significantly improved as compared with that in the control group 14 d after MCAO (P＜0.05). Conclusion ADAS cells can migrate into the ischemic hemisphere and differentiate into neuron-like and astrocytic-like cells after the injection by venous approach in the rat models with MCAO. The intravenous administration of ADAS cells into rats with MCAO leads to good functional outcome and few lesion sizes.