Chen Bin, Ni Yanhong, Liu Jiaying, Zhang Yangheng, Yan Fuhua
Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China.
Center Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China.
Stem Cells Int. 2018 Jul 24;2018:8348121. doi: 10.1155/2018/8348121. eCollection 2018.
Mesenchymal stem cells (MSCs) and their secreted molecules have shown great potential for tissue regeneration and the treatment of inflammation and autoimmune diseases. However, they can also be associated with therapeutic failure or even side effects. Possible causes for this could include the state of the stem cells themselves and the influence of the local microenvironment, wherein macrophages play important roles. As such, we utilized conditioned medium from bone marrow-derived MSCs (MSC-CM) and studied its effect on different macrophage subsets. Effects on macrophage proliferation, apoptosis, polarization, and phagocytosis were determined, and it was discovered that MSC-CM had no significant effect on macrophage proliferation but inhibited M0 macrophage apoptosis and marginally induced M1 macrophage apoptosis. MSC-CM was shown to reduce CD80 expression on the surface of M1 macrophages. Moreover, it promoted and inhibited CD163 expression on the surface of M0 and M1 macrophages, respectively. However, MSC-CM tended to initially promote CD163 expression on M2 macrophages but inhibited expression of this marker after additional incubation time. Unlike MSCs, MSC-CM had no significant effect on the expression of TNF- and IL-10 in macrophages. Thus, the effect of MSC-CM on different types of macrophages is different, and after stem cells are implanted, their effects on the local immune microenvironment are closely related to the original immune status of the implantation site. Therefore, we suggest that when utilizing stem cells for therapeutics, the immune status of the treatment site should be fully elucidated.
间充质干细胞（MSCs）及其分泌分子在组织再生以及炎症和自身免疫性疾病治疗方面展现出了巨大潜力。然而，它们也可能与治疗失败甚至副作用相关。造成这种情况的可能原因包括干细胞自身的状态以及局部微环境的影响，其中巨噬细胞发挥着重要作用。因此，我们利用骨髓源性间充质干细胞的条件培养基（MSC-CM），并研究了其对不同巨噬细胞亚群的影响。测定了对巨噬细胞增殖、凋亡、极化和吞噬作用的影响，发现MSC-CM对巨噬细胞增殖无显著影响，但抑制M0巨噬细胞凋亡，并轻微诱导M1巨噬细胞凋亡。结果显示，MSC-CM可降低M1巨噬细胞表面CD80的表达。此外，它分别促进和抑制M0和M1巨噬细胞表面CD163的表达。然而，MSC-CM最初倾向于促进M2巨噬细胞表面CD163的表达，但在延长孵育时间后会抑制该标志物的表达。与间充质干细胞不同，MSC-CM对巨噬细胞中TNF-和IL-10的表达无显著影响。因此，MSC-CM对不同类型巨噬细胞的作用不同，干细胞植入后，它们对局部免疫微环境的影响与植入部位的原始免疫状态密切相关。所以，我们建议在利用干细胞进行治疗时，应充分阐明治疗部位的免疫状态。
