摘要
目的探讨大鼠骨髓间充质干细胞(rMSCs)向多巴胺能神经元分化条件及其体内修复大鼠帕金森模型的潜能。方法为了能够更好修复大鼠单侧下丘脑-黑质部位注射6-OHDA所造成的功能毁损,我们从SD大鼠中提取了rMSCs。首先利用中药麝香多肽-1诱导rMSCs在体外无血清培养基中扩增并分化为神经元样细胞,然后移植到单侧纹状体区DA耗竭的大鼠模型中。结果加入麝香多肽-1后2 h,细胞开始分化成神经元样细胞,细胞团呈NSE及NF-H阳性。移植后动物模型较对照组有明显的功能改善(P<0．001),表现为25只实验鼠阿普吗啡诱导的旋转减轻,平均持续56 d。免疫组织化学分析证实大量来自rMSCs的细胞在移植带存活并可迁移到距损伤处5 mm的部位,通过检测多巴胺能神经元特异性标志TH发现大约50％～55%细胞继续向多巴胺能神经元方向分化。结论以上发现说明rMSCs来源的细胞移植到大鼠纹状体区后能够存活、迁移、并自发向多巴胺分泌细胞分化,并能修复源自于中脑多巴胺能神经元的功能。
Objective To investigate the factors ofrMSCs differentiation into dopamine-producing cells and its recovery potential of rat Parkinson model in vivo, Methods To better repair the 6-hydroxydopamine （6-OHDA） unilateral lesioned dysfunction in the substantia nigra of rats, rMSCs was prepared from adult Sprague-Dawley （SD） rat, They were firstly proliferated and differentiated in vitro into neuron-like cells in serum-free medium with a Chinese medicine, Musk＇s polypeptide named Musk-1, then grafted into Parkinson rats that had unilateral Dopaminergic （DA） - depleted striatum. Results 2 h after Musk-1 was added, cells started to differentiate into neuron-like cells, making those cell spheres nestin, NSE, NF-H positive. After cell implantation, animals promoted significant improvement in function （apomorphine-induced rotation ameliorated in 25 grafted animals and persisted for 56 days on average） compared to the lesion-control group （P〈0.001）. Histological analysis confirmed a large number of rMSCs-derived cells survived well in the transplantation zoon and migrated around the host lesion as far as 5 millimeters, followed by developing into DA neuron phenotype on approximately 50%-55% of overall cells tested by the DA neuron marker tyrosine hydroxylase （TH）. Conclusion These findings demonstrated that grafted rMSCs-derived cells can survive, migrate, and spontaneously develop into Dopamine-producing cells in striatum and restore behavioral properties of neurons expected from the midbrain.
出处
《中华神经医学杂志》
CAS
CSCD
2006年第4期342-348,共7页
Chinese Journal of Neuromedicine
基金
国家自然科学基金(30370509,30570645)
留学回国人员基金(2003-406)
