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

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。

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＆#39;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-1βin 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＆#39;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.