应用骨髓间充质干细胞治疗自身免疫性重症肌无力研究在哈尔滨医科大学取得新突破,为重症肌无力患者的临床治疗提供了实验基础和理论依据。这一最新研究成果近期发表于德国国际期刊《欧洲免疫学》、美国国际期刊《神经免疫学》和英国国际期刊《免疫学》上。
重症肌无力是神经系统自身免疫性疾病,也是临床的难治性疾病之一,迄今尚无有效、特异的治愈手段。以往较为公认的重症肌无力发病机制与Th1和Th2辅助性T细胞功能失衡有关。哈尔滨医科大学神经生物学教研室主任李呼伦教授带领的科研小组,在实验性自身免疫性重症肌无力的科研工作中,首次提出并证实Th1、Th2、Treg、Th17四种CD4+辅助性T细胞的功能失衡是重症肌无力发病的重要因素,并以此为理论依据,以骨髓间充质干细胞移植治疗作为手段进行了尝试性治疗。
该课题组以人类重症肌无力的大鼠实验动物模型作为研究对象,通过尾静脉大剂量回输骨髓间充质干细胞,并对实验动物进行临床症状评定,发现和证实了重症肌无力的发生、发展与四种细胞亚群格局的改变有关。
据李呼伦教授介绍,骨髓间充质干细胞不仅仅具有组织修复功能,同时由于其具有旁分泌细胞因子效应,因此可以应用于自身免疫性疾病等免疫系统紊乱性疾病的治疗中去,并且由于其可以来自于自体,避免了移植排斥和伦理道德等问题,不仅为人类干细胞移植治疗自身免疫性重症肌无力提供了一个很好的治疗手段,同时为其他自身免疫性疾病的治疗提供了新思路。(生物谷Bioon.com)
生物谷推荐原文出处:
Journal of Clinical Neuroscience doi:10.1016/j.jocn.2009.10.013
In vitro differentiation of bone marrow stromal cells into neurons and glial cells and differential protein expression in a two-compartment bone marrow stromal cell/neuron co-culture system
Xu Qia, Ming Shaob, , , Haisheng Pengc, Zhenggang Bib, Zhiqiang Sua and Hulun Lid
a Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, China
b Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China
c Department of Pharmacy, Daqing Campus, Harbin Medical University, Harbin, China
d Department of Bio-neurology, Harbin Medical University, Harbin, China
This study was performed to establish a bone marrow stromal cell (BMSC)/neuron two-compartment co-culture model in which differentiation of BMSCs into neurons could occur without direct contact between the two cell types, and to investigate protein expression changes during differentiation of this entirely BMSC-derived population. Cultured BMSCs isolated from Wistar rats were divided into three groups: BMSC culture, BMSC/neuron co-culture and BMSC/neuron two-compartment co-culture. Cells were examined for neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) expression. The electrophysiological behavior of the BMSCs was examined using patch clamping. Proteins that had significantly different expression levels in BMSCs cultured alone and co-cultured with neurons were studied using a protein chip–mass spectroscopy technique. Expression of NSE and GFAP were significantly higher in co-culture cells than in two-compartment co-culture cells, and significantly higher in both co-culture groups than in BMSCs cultured alone. Five proteins showed significant changes in expression during differentiation: TIP39_RAT and CALC_RAT underwent increases, and INSL6_RAT, PNOC_RAT and PCSK1_RAT underwent decreases in expression. We conclude that BMSCs can differentiate into neurons during both contact co-culture with neurons and two-compartment co-culture with neurons. The rate at which BMSCs differentiated into neurons was higher in contact co-culture than in non-contact co-culture.