Department of Pharmacy, Liaocheng University, Shandong, 252000, People's Republic of China; Stem Cell Clinical Research Laboratory, Institute for Stem Cell Clinical Research, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, People's Republic of China.
Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China.
Immunol Lett. 2020 Jun;222:49-57. doi: 10.1016/j.imlet.2020.03.005. Epub 2020 Mar 18.
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-1MSCs 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.
间充质干细胞（MSCs）因其低免疫原性和免疫调节特性，成为许多临床应用再生医学中极具吸引力的候选者之一。我们之前的研究表明，小鼠骨髓来源的 Sca-1MSCs 可以从造血祖细胞（HPCs）中诱导调节性 DC（regDCs）（Scal-1 BM-MSC 驱动的 DC[sBM-DCs]）分化，而 Notch 途径在维持其免疫调节特性方面起着关键作用。然而，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-MSCs 表达高水平的 Jagged1，而 sBM-DCs 表达高水平的 Notch1。BM-MSCs 表面表达的 Jagged1 启动 Notch 信号，以维持 sBM-DCs 的免疫调节特性。TGF-β 无论是单独存在还是与 HPCs 培养基共培养，在 MSCs 中的水平都很高。TGF-β 在 sBM-DCs 的增殖和分化中起着至关重要的作用，抑制 TGF-β 会减少生成细胞的数量，并增加 CD34、CD117、CD135 的百分比。因此，MSCs 通过 Notch 信号通路和 TGF-β 协同作用从 HPCs 诱导出 regDCs。这项研究进一步加深了我们对 MSCs 免疫调节机制和潜在治疗功效的理解。
