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人胚胎间充质干细胞通过调节Th7细胞分化减轻MRL/Lpr小鼠的病理变化。

Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation.

作者信息

Yuan Li, Xiao Zhuo-Tao, Huang Xin-Zhong, Wu Min-Juan, Shi Hui, Liu Ai-Fen

机构信息

a Division of Nephrology , Affiliated Hospital of Nantong University , Nantong , Jiangsu Province , China.

b Research Center of Developmental Biology and Department of Histology and Embryology , Second Military Medical University , Shanghai , China.

出版信息

Ren Fail. 2016 Oct;38(9):1432-1440. doi: 10.3109/0886022X.2015.1136894. Epub 2016 Jul 15.

Abstract

Recent evidence indicates that mesenchymal stem cells (MSC) derived from early embryonic tissues have better therapeutic ability as compared with adult tissue-derived stem cells. In the present study, we transplanted human early embryonic MSC (hMSC) into MRL/Lpr mice via tail vein injection to observe the therapeutic efficacy of hMSC and their impact on T helper 17 (Th17) cell differentiation in MRL/Lpr mice. Animals in hMSC treatment group received hMSC (1 × 10/200 μL) via the tail vein at the age of 16 and 19 weeks. We found that hMSC treatment prolonged the survival of MRL/Lpr mice without inducing tumorigenesis, reduced urine protein, and alleviated the renal pathologic changes. In addition, it reduced the proportion of Th17 cells in the spleen of MRL/Lpr mice and the serum interleukin 17 (IL-17) concentration. Our in vitro experiment also demonstrated that hMSC could secrete Th17 differentiation-related cytokines of PGE2, IL-10 and TGF-β, and IFN-γ stimulation up-regulated the secretion of these immune regulating factors. The results of the present study suggest that hMSC therapy could alleviate systemic and local renal lesions in MRL/Lpr mice, probably by secreting immune regulating factors and regulating Th17 cell differentiation in MRL/Lpr mice.

摘要

最近的证据表明,与成体组织来源的干细胞相比,源自早期胚胎组织的间充质干细胞(MSC)具有更好的治疗能力。在本研究中,我们通过尾静脉注射将人早期胚胎MSC(hMSC)移植到MRL/Lpr小鼠体内,以观察hMSC的治疗效果及其对MRL/Lpr小鼠中辅助性T细胞17(Th17)细胞分化的影响。hMSC治疗组的动物在16周和19周龄时通过尾静脉接受hMSC(1×10/200μL)。我们发现,hMSC治疗可延长MRL/Lpr小鼠的生存期,且不会诱导肿瘤发生,可降低尿蛋白水平,并减轻肾脏病理变化。此外,它还降低了MRL/Lpr小鼠脾脏中Th17细胞的比例以及血清白细胞介素17(IL-17)的浓度。我们的体外实验还表明,hMSC可分泌与Th17分化相关的细胞因子PGE2、IL-10和TGF-β,并且IFN-γ刺激可上调这些免疫调节因子的分泌。本研究结果表明,hMSC治疗可能通过分泌免疫调节因子和调节MRL/Lpr小鼠中Th17细胞的分化来减轻MRL/Lpr小鼠的全身和局部肾脏病变。

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