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

Comparison of immunomodulatory properties of exosomes derived from bone marrow mesenchymal stem cells and dental pulp stem cells
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DOI:
10.1007/s12026-019-09088-6
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发表时间:
2019-10-01
影响因子:
4.4
通讯作者:
Feng, Xingmei
Feng, Xingmei
中科院分区:
医学4区
文献类型:
--
作者:
Ji, Lujun;Bao, Liuliu;Feng, Xingmei

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大量发现表明,从多种来源的干细胞释放的外泌体可以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exosomes的免疫抑制作用已被广泛认识,但牙髓干细胞(DPSCs-E)分泌的exosomes在医学免疫领域的研究报道较少。因此,本研究的目的是比较BMMSCs-E和DPSCs-E的免疫调节能力。分别与外周血单个核细胞(PBMCs)共培养,检测到调节性T细胞(Treg)比例增加。随后,我们用BMMSCs-E和DPSCs-E刺激CD 4 +T细胞,观察它们对CD 4 +T细胞极化、趋化因子分泌、凋亡和增殖的影响。我们发现DPSCs-E抑制了CD 4 +T细胞向辅助性T细胞17(Th 17)的分化,减少了促炎因子IL-17和TNF-α的分泌,同时促进了CD 4 +T细胞向Treg的极化,增加了抗炎因子IL-10和TGF-β的释放。此外,DPSCs-E的这些能力比BMMSCs-E强。此外,DPSCs-E诱导CD 4 +T细胞凋亡的作用强于BMMSCs-E,且DPSCs-E对CD 4 +T细胞增殖的抑制作用与BMMSCs-E相似。结论:DPSCs-E比BMMSCs-E具有更强的免疫调节活性,有望成为治疗免疫性疾病的新工具。
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-alpha, while promoted the polarization of CD4+T cells into Treg and increased the release of anti-inflammatory factors IL-10 and TGF-beta. 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.