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比较骨髓间充质干细胞和牙髓干细胞来源的外泌体的免疫调节特性。

Comparison of immunomodulatory properties of exosomes derived from bone marrow mesenchymal stem cells and dental pulp stem cells.

机构信息

Department of Stomatology, Nantong Tongzhou People's Hospital, Nantong, 226001, China.

Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.

出版信息

Immunol Res. 2019 Oct;67(4-5):432-442. doi: 10.1007/s12026-019-09088-6.

Abstract

Substantial discoveries suggested that exosomes released from multiple sources of stem cells can affect the biological functions of target cells. In present period, the immunosuppressive properties of exosomes derived from bone marrow mesenchymal stem cells (BMMSCs-E) have been extensively recognized, but few studies have been reported about exosomes secreted from dental pulp stem cells (DPSCs-E) in the field of medical immunity. Hence, the aim of this study is to compare the immunomodulatory capacity of BMMSCs-E and DPSCs-E. Peripheral blood mononuclear cells (PBMCs) were co-cultured with them respectively and the proportion of regulatory T cells (Treg) was detected to increase. Subsequently, we stimulated CD4+T cells with BMMSCs-E and DPSCs-E to observe their effects on the polarizations, chemokines secretion, apoptosis, and proliferation of CD4+T cells. We found that DPSCs-E inhibited the differentiation of CD4+T cells into T helper 17 cells (Th17) and reduced the secretions of pro-inflammatory factors IL-17 and TNF-α, while promoted the polarization of CD4+T cells into Treg and increased the release of anti-inflammatory factors IL-10 and TGF-β. What's more, these capabilities of DPSCs-E were stronger than those of BMMSCs-E. In addition, DPSCs-E were more effective in inducing apoptosis of CD4+T cells compared with BMMSCs-E, and DPSCs-E inhibited the proliferation of CD4+T cells, which is similar to BMMSCs-E. We draw a conclusion that DPSCs-E have stronger immune-modulating activities than BMMSCs-E, and may be a new therapeutic tool for the treatment of immunological diseases.

摘要

大量研究表明,来源于多种干细胞的外泌体能够影响靶细胞的生物学功能。目前,骨髓间充质干细胞(BMMSCs-E)来源的外泌体的免疫抑制特性已得到广泛认可,但在医学免疫领域,关于牙髓干细胞(DPSCs-E)分泌的外泌体的研究报道甚少。因此,本研究旨在比较 BMMSCs-E 和 DPSCs-E 的免疫调节能力。分别将其与外周血单个核细胞(PBMCs)共培养,检测调节性 T 细胞(Treg)的比例增加。随后,我们用 BMMSCs-E 和 DPSCs-E 刺激 CD4+T 细胞,观察它们对 CD4+T 细胞的极化、趋化因子分泌、凋亡和增殖的影响。我们发现,DPSCs-E 抑制 CD4+T 细胞向辅助性 T 细胞 17 细胞(Th17)的分化,并减少促炎因子 IL-17 和 TNF-α的分泌,同时促进 CD4+T 细胞向 Treg 的极化,并增加抗炎因子 IL-10 和 TGF-β的释放。此外,DPSCs-E 的这些能力强于 BMMSCs-E。此外,与 BMMSCs-E 相比,DPSCs-E 更有效地诱导 CD4+T 细胞凋亡,并且抑制 CD4+T 细胞增殖,这与 BMMSCs-E 相似。我们得出结论,DPSCs-E 具有比 BMMSCs-E 更强的免疫调节活性,可能成为治疗自身免疫性疾病的新治疗工具。

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