Effects of mesenchymal stem cells from human induced pluripotent stem cells on differentiation, maturation, and function of dendritic cells.
Effects of mesenchymal stem cells from human induced pluripotent stem cells on differentiation, maturation, and function of dendritic cells.
复制标题
人诱导多能干细胞间充质干细胞对树突状细胞分化、成熟和功能的影响
DOI：
10.1186/s13287-017-0499-0
复制
发表时间：
2017-03-02
影响因子：
7.5
通讯作者：
Fu QL
中科院分区：
文献类型：
--
作者：
Gao WX;Sun YQ;Shi J;Li CL;Fang SB;Wang D;Deng XQ;Wen W;Fu QL
背景间充质干细胞（mesenchymal stem cells，MSCs）对多种免疫细胞具有强大的免疫调节作用，在治疗免疫性疾病方面具有巨大的潜力。诱导性多能干细胞（iPSCs）是一种无限制的、非侵入性的间充质干细胞来源，iPSC-MSCs具有更多的优势，对T淋巴细胞和自然杀伤细胞具有免疫调节作用。然而，iPSC-MSC对树突状细胞（DC）的影响尚不清楚。本研究的目的是探讨iPSC-MSCs对DCs分化、成熟和功能的影响。流式细胞术分析DCs的表型和功能，酶联免疫吸附试验（ELISA）研究细胞因子的产生。ResultsIn this study，我们成功地从不同克隆的人iPSCs中诱导出MSC。iPSC-MSC表现出比BM-MSC更高的增殖率和更少的细胞衰老。iPSC-MSC通过产生白细胞介素（IL）-10和直接细胞接触抑制人单核细胞来源的DC的分化。此外，iPSC-MSC并不影响未成熟DC变成成熟DC，但通过增加其吞噬能力和抑制其刺激淋巴细胞增殖的能力来调节其功能特性。更重要的是，iPSC-MSCs诱导产生的IL-10产生的调节DC的成熟过程中，这主要是由细胞-细胞接触mechanism.ConclusionsOur结果表明，iPSC-MSCs在DC的分化和功能的调制中的重要作用，支持iPSC-MSCs在DC介导的免疫疾病的临床应用。
BackgroundMesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs.MethodsHuman monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production.ResultsIn this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism.ConclusionsOur results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases.