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衰老而非帕金森病影响 PBMC 对骨髓间充质干细胞免疫抑制的反应性。

Aging, rather than Parkinson's disease, affects the responsiveness of PBMCs to the immunosuppression of bone marrow mesenchymal stem cells.

机构信息

Department of Cell Biology, Key laboratory of Ministry of Education, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.

Department of Neurology, The General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.

出版信息

Mol Med Rep. 2019 Jan;19(1):165-176. doi: 10.3892/mmr.2018.9670. Epub 2018 Nov 19.

Abstract

Whether aging or Parkinson's disease (PD) affects the responses of peripheral blood mononuclear cells (PBMCs) to immunosuppression by bone marrow‑derived mesenchymal stem cell (BM‑MSCs) and which cytokines are more effective in inducing BM‑MSCs to be immunosuppressive remains to be elucidated. PBMCs were isolated from healthy young (age 26‑35), healthy middle‑aged (age 56‑60) and middle‑aged PD‑affected individuals. All the recruits were male. The mitogen‑stimulated PBMCs and proinflammatory cytokine‑pretreated BM‑MSCs were co‑cultured. The PBMC proliferation was measured using Cell Counting Kit‑8, while the cytokine secretion was assayed by cytometric bead array technology. The immunosuppressive ability of BM‑MSCs was confirmed in young healthy, middle‑aged healthy and middle‑aged PD‑affected individuals. Among the three groups, the PBMC proliferation and cytokine secretion of the young healthy group were suppressed more significantly compared with those of the middle‑aged healthy and middle‑aged PD‑affected group. No significant differences were identified in the PBMC proliferation and cytokine secretion between the patients with PD and the middle‑aged healthy subjects. Interferon (IFN)‑γ synergized with tumor necrosis factor (TNF)‑α, interleukin (IL)‑1α or IL‑1β was more effective than either one alone, and the combinations of IFN‑γ + IL‑1α and IFN‑γ + IL‑1β were more effective than IFN‑γ + TNF‑α in inducing BM‑MSCs to inhibit PBMC proliferation. The results of the present study suggested that aging, rather than PD, affects the response of PBMCs toward the suppression of BM‑MSC, at least in middle‑aged males. Patients with PD aged 56‑60 remain eligible for anti‑inflammatory BM‑MSC‑based therapy. Treatment of BM‑MSCs with IFN‑γ + IL‑1α or IFN‑γ + IL‑1β prior to transplantation may result in improved immunosuppressive effects.

摘要

无论衰老还是帕金森病(PD)是否会影响骨髓间充质干细胞(BM-MSCs)对周围血单个核细胞(PBMC)的免疫抑制作用,以及哪种细胞因子更有效地诱导 BM-MSCs 产生免疫抑制作用,仍有待阐明。从健康的年轻(年龄 26-35 岁)、健康的中年(年龄 56-60 岁)和中年 PD 患者中分离 PBMC。所有入组者均为男性。将有丝分裂原刺激的 PBMC 和促炎细胞因子预处理的 BM-MSCs 共培养。使用细胞计数试剂盒-8 测量 PBMC 增殖,使用流式细胞术微珠阵列技术测定细胞因子分泌。在年轻健康、中年健康和中年 PD 患者中均证实了 BM-MSCs 的免疫抑制能力。在这三组中,年轻健康组的 PBMC 增殖和细胞因子分泌受到的抑制比中年健康组和中年 PD 组更为显著。PD 患者与中年健康受试者之间的 PBMC 增殖和细胞因子分泌无显著差异。与单独使用 TNF-α、IL-1α 或 IL-1β 相比,IFN-γ 与 TNF-α、IL-1α 或 IL-1β 的联合使用效果更显著,IFN-γ+IL-1α 和 IFN-γ+IL-1β 的联合使用效果比 IFN-γ+TNF-α 更显著,能够诱导 BM-MSCs 抑制 PBMC 增殖。本研究结果表明,至少在中年男性中,衰老而不是 PD 影响 PBMC 对 BM-MSC 抑制的反应。56-60 岁的 PD 患者仍适合接受抗炎性 BM-MSC 为基础的治疗。在移植前用 IFN-γ+IL-1α 或 IFN-γ+IL-1β 处理 BM-MSCs 可能会导致免疫抑制作用得到改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cc0/6297737/8214d9c7cdae/MMR-19-01-0165-g00.jpg

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