人骨髓间充质干细胞源性神经元样细胞移植治疗局灶性脑缺血后神经功能障碍的实验研究

Experimental Study on the Effects of Human Bone Mesendymal Stem Cells(hBMSCs) Neuron-like Cells Transplantation into Local Cerebral Ischemic Rats

目的探讨人骨髓间充质干细胞(hBMSCs)源性神经元样细胞移植对局灶性脑缺血后神经功能缺失的治疗作用。方法应用胶氧尿苷(Brdu)标记全反式维甲酸联合细胞因子诱导的hBMSCs源性神经元样细胞,通过立体定向分别将磷酸盐缓冲液(BS)、hBMSCs及hBMSCs源性神经元样细胞植入局灶性脑缺血模型大鼠纹状体内。观察移植后各组大鼠神经功能恢复情况。结果hBMSCs和hBMSCs源性神经元样组术后神经损伤严重缺损评分(NSS)、平衡木试验(BBT)、一次性被动回避平台试验(SDPAT)、水迷宫试验(WMT)较PBS组显著好转(P<0.01);hBMSCs组术后1、3周NSS、BBT较hBMSCs源性神经元样组明显好转(P<0.05),术后6、8周两组比较差异无统计学意义(P>0.05);hBMSCs源性神经元样组SDPAT、WMT较hBMSCs组改善明显(P<0.05)。结论hBMSCs和hBMSCs源性神经元样细胞脑内移植均能有效改善局灶性脑缺血大鼠的神经功能症状,hBMSCs移植作用快,而hBMSCs源性神经元样细胞移植在学习、记忆功能方面改善更好,可能是治疗局灶性脑缺血的一种方法。

Objective To explore the effects of hBMSCs neuron-like cell transplantation on the repair of neurological functions with local cerebral ischemic rats. Methods hBMSCs were induced towards neuro-like cells with ATRA and focal cerebral ischemia was induced by transient MCAO with a monofilament suture in adult Wistar rats. HBMSCs marked by Brdu and neuron-like cells from hBMSC marked by BrdU were transplanted into rats＇ striatum by stereotactic operation. The behaviors of animals were observed. Then histological examinations were also performed. Results The NSS, BBT, SDPAT, WMT in the group hBMSCs and hBMSCs neuro-like cells are much better than that in the group PBS （P 〈0.01 ）. The NSS, BBT in the group hBMSCs are better than that in the group of hBMSCs neuro-like cells at the 1^ st, 3^rd week after operation （P 〈 0.05 ）, and there was no statistics difference at the 6^th, 8^th week. The SDPAT and WMT of group hBMSCs neuro-like cells are much better than that in the group hBMSCs （P 〈 0.05）. Conclusion In the two groups of hBMSCs and hBMSCs neuro-like cells both can improve the neurological function of the focal cerebral ischemia rats effectively, but hBMSCs have faster effect than the others. The transplantation effect on improving study and memory in the group of hBMSCs neuro-like cells is better than that in the hBMSCs group. The intra-cerebral transplantation in the neuron-like cells from hBMSCs would be one of measures for treatment of local cerebral ischemia.