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毒胡萝卜素处理的间充质干细胞分泌的细胞外囊泡通过增强免疫调节特性改善实验性结肠炎。

Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties.

作者信息

Joo Hansol, Oh Mi-Kyung, Kang Ji Yeon, Park Hyun Sung, Chae Dong-Hoon, Kim Jieun, Lee Jong-Hee, Yoo Hee Min, Choi Uimook, Kim Do-Kyun, Lee Hakmo, Kim Sungjoo, Yu Kyung-Rok

机构信息

Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

出版信息

Biomedicines. 2021 Feb 18;9(2):209. doi: 10.3390/biomedicines9020209.

DOI:10.3390/biomedicines9020209
PMID:33670708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7922639/
Abstract

Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)-primed human Wharton's jelly-derived MSCs (WJ-MSCs). EVs from TSG-primed WJ-MSCs (TSG-EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor-β1 (TGFβ), cyclooxygenase-2 (COX2), and especially indoleamine 2,3-dioxygenase (IDO), compared to control EVs. TSG-EV showed a significantly enhanced immunosuppressive effect on human peripheral blood-derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2-type macrophage were enriched compared to a control EV-treated group. Furthermore, TSG-EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2-type macrophages in colitic colons of a TSG-EV-treated mouse suggests an anti-inflammatory effect of TSG-EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ-MSCs, and TSG-EV may provide a new therapeutic approach for treatment of colitis.

摘要

间充质干细胞（MSC）来源的细胞外囊泡（EV）因其对免疫介导的炎症性疾病的免疫调节特性而备受关注。在此，我们证明了内质网（ER）应激诱导剂毒胡萝卜素（TSG）预处理的人脐带华通氏胶来源的间充质干细胞（WJ-MSC）分泌的EV具有增强的免疫调节特性。与对照EV相比，TSG预处理的WJ-MSC来源的EV（TSG-EV）显示出免疫调节因子产量增加以及转化生长因子-β1（TGFβ）、环氧合酶-2（COX2），尤其是吲哚胺2,3-双加氧酶（IDO）的表达增加。TSG-EV对人外周血来源的T细胞增殖以及Th1和Th17分化显示出显著增强的免疫抑制作用，而与对照EV处理组相比，Treg和M2型巨噬细胞增多。此外，TSG-EV通过减轻炎症反应和维持肠道屏障完整性，显著减轻了小鼠实验性结肠炎。TSG-EV处理的小鼠结肠炎结肠中Tregs和M2型巨噬细胞显著增加，表明TSG-EV在结肠炎模型中具有抗炎作用，可能是由Treg和巨噬细胞极化介导的。这些数据表明，TSG处理促进了WJ-MSC来源的EV的免疫调节特性，并且TSG-EV可能为结肠炎的治疗提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/7593f55bfcc8/biomedicines-09-00209-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/e2526c76de2a/biomedicines-09-00209-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/361ff690ff4a/biomedicines-09-00209-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/ee55d6994e67/biomedicines-09-00209-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/e8cc8795eead/biomedicines-09-00209-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/7593f55bfcc8/biomedicines-09-00209-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/e2526c76de2a/biomedicines-09-00209-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/361ff690ff4a/biomedicines-09-00209-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/ee55d6994e67/biomedicines-09-00209-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/e8cc8795eead/biomedicines-09-00209-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7922639/7593f55bfcc8/biomedicines-09-00209-g005.jpg

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