人羊膜上皮细胞移植及基因治疗帕金森病大鼠

观察人羊膜上皮细胞(human amniotic epithelial cell,HAEC及)人脑源性神经营养因子(brain-derived neurotrophic factor,BDNF基)因修饰的HAEC在帕金森病(Parkinson’sdisease,PD)模型大鼠脑内的长期存活和对旋转行为的治疗效果。用包装BDNFcDNA的慢病毒转染原代HAEC(HAEC/BDNF),HAEC/BDNF与HAEC分别植入6-羟基多巴胺损伤的PD模型大鼠纹状体内,观察动物的旋转行为,用免疫组织化学方法鉴定移植物在体内的存活。结果表明,治疗组PD大鼠的旋转行为改善明显达14周,HAEC/BDNF组能使恢复时间提前。免疫组织化学方法发现移植细胞在14周后仍有少量存活且部分表达BDNF、酪氨酸羟化酶,纹状体内星形胶质细胞增生。实验结果说明,HAEC和BDNF基因修饰的HAEC移植对PD模型大鼠的行为有一定改善,HAEC可以作为一种治疗PD的供体细胞。

Transplantation of Human Amniotic Epithelial Cells and Genetically Modified Cells for the Treatment of Parkinsonian Rats

To investigate the long-term graft survival and the improvement of motor abnormalities after the intracerebral transplantation of the human amniotic epithelial cells (HAEC) and HAECs modified with human brain-derived neurotrophic factor (BDNF) cDNA in the rat model of Parkinson's disease (PD). Primary HAECs and BDNF genetically modified HAECs (HAECs/BDNF) transferred with lentiviral vectors were transplanted into the striatum of rats after the 6-hydroxydopamine lesion. We observed the rotational behavior and detected the graft survival by immunohistochemistry. The result showed that the asymmetric rotational behavior of transplanted PD rats significantly improved for 14 weeks while the initial recovery time of HAECs/BDNF group was shorter than that of HAECs group. A few cells could survive for 14 weeks in vivo, and some were BDNF, TH positive. In addition, the reactivity of astrocytes increased in the rat striatum of treatment groups. This study indicated that the behavioral amelioration of PD model rats can be achieved by transplanting HAECs and BDNF genetically modified HAECs. HAECs may be used as effective donor cells for the treatment of PD.