Human infrapatellar fat pad mesenchymal stem cells show immunomodulatory exosomal signatures.
Human infrapatellar fat pad mesenchymal stem cells show immunomodulatory exosomal signatures.
复制标题
人的膝下脂肪垫间充质干细胞表现出免疫调节的胞外信号。
DOI：
10.1038/s41598-022-07569-7
复制
发表时间：
2022-03-04
影响因子：
4.6
通讯作者：
Best TM
中科院分区：
文献类型：
--
作者：
Kouroupis D;Kaplan LD;Best TM
在人膝髌下脂肪垫（IFP）和滑膜内，驻留的滑膜细胞和巨噬细胞参与炎症性关节疾病的发生和进展。我们的假设是，ifp衍生的间充质干细胞（IFP-MSC）强大的免疫调节治疗作用主要是通过其外泌体（IFP-MSC EXOs）分泌组通过减弱滑膜细胞和巨噬细胞的促炎激活来发挥的。IFP-MSC exo显示出不同的miRNA和蛋白质免疫调节谱。外泌体中高度存在的24个mirna的反应组分析显示，它们参与了包括免疫系统在内的六个基因群的调节。外泌体富含免疫调节和修复蛋白，这些蛋白参与细胞增殖、刺激反应、信号转导、信号受体活性和蛋白磷酸化的积极调节。与单独刺激相比，暴露于IFP-MSC exo的刺激滑膜细胞或巨噬细胞的增殖明显减少，炎症相关分子谱改变，促炎分子分泌减少。在急性滑膜/IFP炎症大鼠模型中，IFP- msc EXOs治疗导致滑膜/IFP组织内巨噬细胞向抗炎治疗M2表型强烈极化。基于这些发现，我们提出了一种可行的无细胞替代msc为基础的治疗方法，作为治疗滑膜炎和IFP纤维化的替代方法。
Within the human knee infrapatellar fat pad (IFP) and synovium, resident synoviocytes and macrophages contribute to the onset and progression of inflammatory joint diseases. Our hypothesis is that IFP-derived mesenchymal stem cells (IFP-MSC) robust immunomodulatory therapeutic effects are largely exerted via their exosomal (IFP-MSC EXOs) secretome by attenuating synoviocytes and macrophages pro-inflammatory activation. IFP-MSC EXOs showed distinct miRNA and protein immunomodulatory profiles. Reactome analysis of 24 miRNAs highly present in exosomes showed their involvement in the regulation of six gene groups, including immune system. Exosomes were enriched for immunomodulatory and reparative proteins that are involved in positive regulation of cell proliferation, response to stimulus, signal transduction, signal receptor activity, and protein phosphorylation. Stimulated synoviocytes or macrophages exposed to IFP-MSC EXOs demonstrated significantly reduced proliferation, altered inflammation-related molecular profiles, and reduced secretion of pro-inflammatory molecules compared to stimulated alone. In an acute synovial/IFP inflammation rat model, IFP-MSC EXOs therapeutic treatment resulted in robust macrophage polarization towards an anti-inflammatory therapeutic M2 phenotype within the synovium/IFP tissues. Based on these findings, we propose a viable cell-free alternative to MSC-based therapeutics as an alternative approach to treating synovitis and IFP fibrosis.
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DOI：
10.3390/bioengineering8110166
发表时间：
2021-10-29
期刊：
Bioengineering (Basel, Switzerland)
影响因子：
--
作者：
Kouroupis D;Best TM;Kaplan LD;Correa D;Griswold AJ
通讯作者：
Griswold AJ
影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
8.8
作者：
Chinnadurai R;Rajan D;Qayed M;Arafat D;Garcia M;Liu Y;Kugathasan S;Anderson LJ;Gibson G;Galipeau J
通讯作者：
Galipeau J
影响因子：
6
作者：
Hindle, Paul;Khan, Nusrat;Peault, Bruno
通讯作者：
Peault, Bruno
影响因子：
13.3
作者：
Eymard, Florent;Pigenet, Audrey;Houard, Xavier
通讯作者：
Houard, Xavier