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The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome.
Stem Cells International ( IF 3.8 ) Pub Date : 2020-07-18 , DOI: 10.1155/2020/4058760
Adriana Cifù 1, 2 , Rossana Domenis 1 , Massimo Pozzi-Mucelli 3 , Paolo Di Benedetto 4 , Araldo Causero 4 , Massimo Moretti 5 , Marta Stevanato 1 , Cinzia Pistis 2 , Pier Camillo Parodi 6 , Martina Fabris 1, 2 , Francesco Curcio 1, 2
Affiliation  

Objective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interaction with the inflammatory microenvironment seems to have a critical role. Design. To reproduce the inflammatory microenvironment, AMSCs were exposed to osteoarthritic synovial fluid (SF) for 48 h and the effect of their secretome on differentiation of monocytes (M0) into macrophages M1-like and mature dendritic cells (mDCs) was evaluated. Furthermore, the effect of the secretome of AMSCs exposed to SF was evaluated on the T cell population in terms of T cell proliferation and expansion of T regulatory cells (T reg). Results. Our data show that the exposure of AMSCs to SF activates cells and promotes the release of immunosuppressive factors, which induce macrophage polarization of M0 into the M2-like phenotype and inhibit differentiation of monocytes into mature dendritic cells (mDCs). Only the secretome of exposed AMSCs was able to inhibit T cell proliferation and promote T reg expansion. Conclusions. Our results suggest that the microenvironment plays a fundamental role for the development of anti-inflammatory and immunomodulatory properties of AMSCs.

中文翻译:

骨关节炎滑液的暴露增强了脂肪间充质干细胞分泌组的免疫调节特性。

客观。几项临床研究提出了注入脂肪间充质干细胞 (AMSCs) 作为具有炎症成分的关节疾病(如骨关节炎)的替代疗法。事实上,AMSCs 能够通过旁分泌活动刺激组织修复,并且与炎症微环境的相互作用似乎具有关键作用。设计. 为了重现炎症微环境,将 AMSCs 暴露于骨关节炎滑液 (SF) 48 小时,并评估其分泌组对单核细胞 (M0) 分化为巨噬细胞 M1 样和成熟树突状细胞 (mDCs) 的影响。此外,在 T 细胞增殖和 T 调节细胞 (T reg) 扩增方面,评估了暴露于 SF 的 AMSCs 的分泌组对 T 细胞群的影响。结果. 我们的数据表明,AMSCs 暴露于 SF 可激活细胞并促进免疫抑制因子的释放,从而诱导 M0 巨噬细胞极化为 M2 样表型,并抑制单核细胞分化为成熟树突状细胞 (mDCs)。只有暴露的 AMSCs 的分泌组能够抑制 T 细胞增殖并促进 T reg 扩增。结论。我们的研究结果表明,微环境对 AMSCs 的抗炎和免疫调节特性的发展起着重要作用。
更新日期:2020-07-18
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