Implantation of chondrogenically differentiated mesenchymal stromal cells (MSCs) leads to bone formation in vivo through the process of endochondral ossification. The use of allogeneic MSCs for this purpose may be a promising new approach to replace the current gold standard of bone regeneration. However, the success of using allogeneic cells depends on the interaction between the implanted cells and the host's endogenous immune cells. Th17 T cells and other CD4 helper T cell subtypes have been shown to negatively impact chondrogenesis, however, it is unclear how the interaction between these cells affects bone regeneration mediated by these cells. The aim of the current work was to assess the effect of chondrogenic MSC pellets on Th1, Th2, Th17, and regulatory T cells in vitro. Human MSCs were nonchondrogenic (−TGFβ3) and chondrogenically (+TGFβ3) differentiated for 7 or 21 days. Memory T cells (sorted from the CD4 population of peripheral blood mononuclear cells [PBMCs]), as well as total PBMCs were cocultured with allogeneic nonchondrogenic and chondrogenic MSC pellets for 3 days. Seven-day differentiated allogeneic nonchondrogenic and chondrogenic MSC pellets that were cocultured with memory T cells resulted in a significant increase in Th2 and a decrease in Th1 T cells. Furthermore, the co-culture of 21-day differentiated nonchondrogenic and chondrogenic MSC pellets with memory T cells resulted in a significant increase in Th2 and Th17 T cells, as well as a decrease in Th1 and regulatory T cells. Interleukin (IL)-6 was identified as a predominant cytokine involved in this interaction between allogeneic chondrogenically differentiated MSC pellets and memory CD4 T cells, with high levels of IL-6 being secreted in the supernatants of this cocultured condition. The findings of this study highlight the potential of chondrogenically differentiated MSC pellets to alter the ratio of Th1 and Th2 as well as Th17 and regulatory T cell subsets. Additional analysis investigating bone formation by chondrogenically differentiated MSCs in an allogeneic setting may identify a novel role of these T cell subsets in bone regeneration processes mediated by chondrogenically differentiated MSCs.

中文翻译：

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同种异体软骨间质基质细胞改变CD4 +记忆T细胞中的辅助性T细胞亚群。

软骨分化的间充质基质细胞（MSCs）的植入通过软骨内骨化过程导致体内骨形成。为此目的使用同种异体MSC可能是一种有希望的新方法，以取代当前的骨再生金标准。但是，使用同种异体细胞的成功取决于植入的细胞与宿主内源性免疫细胞之间的相互作用。已经显示Th17 T细胞和其他CD4辅助T细胞亚型会对软骨形成产生负面影响，但是，尚不清楚这些细胞之间的相互作用如何影响这些细胞介导的骨再生。当前工作的目的是评估软骨生成MSC沉淀对Th1，Th2，Th17和调节性T细胞的体外作用。人间充质干细胞是非软骨形成的（-TGFβ3），并且是软骨形成的（+TGFβ3）分化7或21天。将记忆T细胞（从外周血单核细胞[PBMC]的CD4群体中分类）以及总PBMC与同种异体非软骨形成和软骨形成MSC沉淀共培养3天。与记忆T细胞共培养的7天分化同种异体非软骨形成和软骨形成MSC沉淀导致Th2的显着增加和Th1 T的减少。此外，21天分化的非软骨形成和软骨形成MSC沉淀与记忆T细胞的共培养导致Th2和Th17 T细胞显着增加，以及Th1和调节性T细胞减少。白细胞介素（IL）-6被确定为同种异体软骨形成分化的MSC沉淀与记忆CD4 T细胞之间这种相互作用的主要细胞因子，在这种共培养条件的上清液中分泌高水平的IL-6。这项研究的结果突出了软骨分化的MSC颗粒改变Th1和Th2以及Th17和调节性T细胞亚群的比例的潜力。在同种异体环境中调查软骨分化的MSC的骨形成的其他分析可能会发现这些T细胞亚群在软骨分化的MSC介导的骨再生过程中的新作用。这项研究的结果突出了软骨分化的MSC颗粒改变Th1和Th2以及Th17和调节性T细胞亚群的比例的潜力。在同种异体环境中调查软骨分化的MSC的骨形成的其他分析可能会发现这些T细胞亚群在软骨分化的MSC介导的骨再生过程中的新作用。这项研究的结果突出了软骨分化的MSC颗粒改变Th1和Th2以及Th17和调节性T细胞亚群的比例的潜力。在同种异体环境中调查软骨分化的MSC的骨形成的其他分析可能会发现这些T细胞亚群在软骨分化的MSC介导的骨再生过程中的新作用。