人脐带间充质干细胞对帕金森病患者外周血淋巴细胞增生的抑制

doi:10.3969/j.issn.1006-7795.2014.03.016

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (3): 344-352.doi: 10.3969/j.issn.1006-7795.2014.03.016

人脐带间充质干细胞对帕金森病患者外周血淋巴细胞增生的抑制

赵春松^1,2, 邹海强³, 闫晓明⁴, 关云谦^1,2, 陈凌⁵, 王佳茵^1,2, 张愚^1,2

1. 首都医科大学宣武医院细胞生物室, 北京 100053;
2. 教育部神经变性病重点实验室, 北京 100053;
3. 广州军区广州总医院神经内科, 广州 510010;
4. 首都医科大学宣武医院功能神经外科, 北京 100053;
5. 首都医科大学宣武医院神经外科, 北京 100053

收稿日期:2013-09-28 发布日期:2014-06-14
通讯作者: 王佳茵，E-mail：jiayyw@sina.com E-mail:jiayyw@sina.com
基金资助:
教育部新教师基金（20091107120004）；北京市科委健康培育项目（Z111107067311033）；北京市科技新星项目（2009B22）；国家973计划（2012CBA01300）；国家863计划（2011AA020106）。

Human umbilical cord mesenchymal stem cells inhibit the proliferation of peripheral blood mononuclear cells in Parkinson’s disease patients

Zhao Chunsong^1,2, Zou Haiqiang³, Yan Xiaoming⁴, Guan Yunqian^1,2, Chen Ling⁵, Wang Jiayin^1,2, Zhang Yu^1,2

1. Department of Cell Biology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
2. Key Laboratory of Neurodegeneration, Ministry of Education, Beijing 100053, China;
3. Department of Neurology, The General Hospital of Guangzhou Military Command in Guangzhou, Guangzhou 510010, China;
4. Department of Function Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
5. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2013-09-28 Published:2014-06-14
Supported by:
This study was supported by Science Foundation for the Youth Scholars, Ministry of Education of China(20091107120004), the Beijing Municipal Science and Technology Commission(Z111107067311033), Beijing Nova Program of Science and Technology(2009B22), National Basic Research Program of China(2012CBA01300), National High Technology Research and Development Program of China(2011AA020106).

摘要/Abstract

摘要：

目的观察人脐带间充质干细胞（umbilical cord mesenchymal stem cells，UC-MSC）对男性健康青年人（25~35岁）、健康中年人（50~60岁）、以及中年帕金森病（Parkinson’s disease，PD）患者的外周血单核细胞（peripheral blood mononuclear cell，PBMC）增生的抑制作用，并探讨引发UC-MSC发挥抑制作用所需要的细胞因子。方法用不同组合的细胞因子作用后的UC-MSC和PBMC共培养，观察PBMC增生受抑制的情况。结果不仅健康青年人的PBMC增生被UC-MSC抑制，健康中年人和中年PD患者的淋巴细胞也受到抑制，PD患者PBMC受抑制程度比青年人小，但和同年龄组健康中年人相比差异没有统计学意义；UC-MSC必须经过肿瘤坏死因子α（tumor necrosis factor，TNFα）、白细胞介素-1α（interleukin-1α，IL-1α）、IL-1β中的一种与干扰素-γ（interferon-γ，IFN-γ）联合刺激后才可以发挥抑制作用，“IFN-γ+IL-1α”和“IFN-γ+IL-1β”组合刺激UC-MSC后对PBMC的抑制作用相比“IFN-γ+TNFα”更强。结论 UC-MSC对PBMC的抑制作用不是自发的，而需要炎性反应因子的刺激，这就提示经过体外炎性反应因子处理的UC-MSC可能更适合移植后抗炎性反应治疗的需要；UC-MSC可以体外抑制PD患者PBMC增生，至少对于中年患者，帕金森病并没有影响PBMC增生对UC-MSC抑制作用的反应性，这就为临床实验治疗PD提供了一项理论依据。

关键词: 脐带, 间充质干细胞, 帕金森病, 炎性反应, 移植

Abstract:

Objective To observe the immune-suppression ability of umbilical cord mesenchymal stem cells(UC-MSC) on the proliferation of peripheral blood mononuclear cells(PBMC), which were isolated from young(25~35 years) healthy, middle aged(50~60 years) healthy, and middle aged PD(Parkinson's disease) individuals and to explore what cytokines are required to induce UC-MSC to be immune-suppressive. Methods All the recruits were males. Co-culture of the PBMCs and the UC-MSC pretreated by different cytokines and measure the proliferation of PBMC were done. Results The immune-suppression ability of UC-MSC was confirmed with young healthy, middle aged healthy, and middle aged PD individuals. In our experiments, IFN-γ synergized with TNFα, IL-1α, or IL-1β in inducing UC-MSCs was proved to inhibit PBMC proliferation. The combinations of "IFN-γ+IL-1α" and "IFN-α+IL-1β" are more powerful than "IFN-γ+TNF-α" in inducing UC-MSC to inhibit the proliferation of PBMC. We also found that the PBMC proliferation of young after UC-MSC co-culture was significantly lower than that of PD patients, but the proliferation of PD patients' PBMC didn't show any difference when compared with middle aged healthy ones. Conclusions All of these results showed that the immune-suppression ability of UC-MSC is not innate, but is cytokine stimulation dependent. Furthermore, the PBMC inhibition of PD patient, together with that the PD progression did not affect the response of PBMC toward the inhibition of UC-MSC, is the direct evidence that UC-MSC might be a candidate cell type in anti-inflammation therapy of PD.

Key words: umbilical cord, mesenchymal stem cells, Parkinson’s disease, inflammation, transplantation

中图分类号:

R741

赵春松, 邹海强, 闫晓明, 关云谦, 陈凌, 王佳茵, 张愚. 人脐带间充质干细胞对帕金森病患者外周血淋巴细胞增生的抑制[J]. 首都医科大学学报, 2014, 35(3): 344-352.

Zhao Chunsong, Zou Haiqiang, Yan Xiaoming, Guan Yunqian, Chen Ling, Wang Jiayin, Zhang Yu. Human umbilical cord mesenchymal stem cells inhibit the proliferation of peripheral blood mononuclear cells in Parkinson’s disease patients[J]. Journal of Capital Medical University, 2014, 35(3): 344-352.

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人脐带间充质干细胞对帕金森病患者外周血淋巴细胞增生的抑制

Human umbilical cord mesenchymal stem cells inhibit the proliferation of peripheral blood mononuclear cells in Parkinson’s disease patients

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