Mesenchymal stem cells (MSCs) are one of the attractive candidates in regenerative medicine of many clinical applications because of their low immunogenicity and immunomodulatory property. Our previous studies provided that mouse bone marrow-derived Sca-1+MSCs could drive the differentiation of regulatory DC (regDCs) (Scal-1+ BM-MSC-driven DC [sBM-DCs]) from hemopoietic progenitor cells (HPCs) and the Notch pathway played a critical role in maintaining the immunomodulatory property. However, the detailed mechanisms of their immunoregulatory capacity are not fully defined. In the present study, we show that BM-MSCs expressed high levels of Jagged 1 while sBM-DCs expressed high levels of Notch1. Jagged1 expressed on the surface of BM-MSCs initiated Notch signaling to maintain the immunomodulatory property of the sBM-DCs. The level of TGF-β is high in MSCs, either alone or coculture with HPCs medium. TGF-β plays a vital role in the proliferation and differentiation of sBM-DCs and inhibition of TGF-β reduce the number and increase the percentage of CD34, CD117, CD135 of generation cells. Thus, MSCs induced the regDCs from HPCs via the Notch signaling pathway and TGF-β synergistically. This study further broadens our understanding of the immunomodulatory mechanism and the potential therapeutic efficacy of MSCs.

中文翻译：

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间充质干细胞通过Notch途径和TGF-β协同诱导造血祖细胞产生的调节性树突状细胞。

间充质干细胞（MSC）由于其低的免疫原性和免疫调节特性，在许多临床应用的再生医学中是有吸引力的候选者之一。我们以前的研究提供了小鼠骨髓来源的Sca-1 + MSCs可以驱动造血祖细胞（HPCs）和Notch途径在维持免疫调节特性中起关键作用。但是，其免疫调节能力的详细机制尚未完全确定。在本研究中，我们表明BM-MSC表达高水平的锯齿状1，而sBM-DCs表达高水平的Notch1。在BM-MSC表面表达的Jagged1启动了Notch信号，以维持sBM-DC的免疫调节特性。单独或与HPC培养基共培养时，MSC中的TGF-β水平较高。TGF-β在sBM-DC的增殖和分化中起着至关重要的作用，抑制TGF-β会减少世代细胞CD34，CD117，CD135的数量并增加其百分比。因此，MSC通过Notch信号通路和TGF-β协同诱导了HPC的regDC。这项研究进一步拓宽了我们对MSCs的免疫调节机制和潜在治疗功效的理解。