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间充质基质细胞通过 miR-29c 和 miR-129 的细胞间转移促进肺纤维化的解决。

Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer.

机构信息

Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation.

Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation.

出版信息

Exp Mol Med. 2023 Jul;55(7):1399-1412. doi: 10.1038/s12276-023-01017-w. Epub 2023 Jul 3.

DOI:10.1038/s12276-023-01017-w
PMID:37394579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10393964/
Abstract

To date, pulmonary fibrosis remains an unmet medical need. In this study, we evaluated the potency of mesenchymal stromal cell (MSC) secretome components to prevent pulmonary fibrosis development and facilitate fibrosis resolution. Surprisingly, the intratracheal application of extracellular vesicles (MSC-EVs) or the vesicle-depleted secretome fraction (MSC-SF) was not able to prevent lung fibrosis when applied immediately after the injury caused by bleomycin instillation in mice. However, MSC-EV administration induced the resolution of established pulmonary fibrosis, whereas the vesicle-depleted fraction did not. The application of MSC-EVs caused a decrease in the numbers of myofibroblasts and FAPa progenitors without affecting their apoptosis. Such a decrease likely occurred due to their dedifferentiation caused by microRNA (miR) transfer by MSC-EVs. Using a murine model of bleomycin-induced pulmonary fibrosis, we confirmed the contribution of specific miRs (miR-29c and miR-129) to the antifibrotic effect of MSC-EVs. Our study provides novel insights into possible antifibrotic therapy based on the use of the vesicle-enriched fraction of the MSC secretome.

摘要

迄今为止,肺纤维化仍然是一种未满足的医学需求。在这项研究中,我们评估了间充质基质细胞(MSC)分泌组成分预防肺纤维化发展和促进纤维化消退的效力。令人惊讶的是,当在博莱霉素滴注引起的损伤后立即应用于小鼠时,细胞外囊泡(MSC-EVs)或囊泡耗尽的分泌组部分(MSC-SF)的气管内应用不能预防肺纤维化。然而,MSC-EV 的给药诱导了已建立的肺纤维化的消退,而囊泡耗尽的部分则没有。MSC-EV 的应用导致肌成纤维细胞和 FAPa 祖细胞数量减少,而不影响其凋亡。这种减少可能是由于 MSC-EVs 通过 microRNA(miR)转移导致其去分化。使用博莱霉素诱导的肺纤维化的小鼠模型,我们证实了特定的 miR(miR-29c 和 miR-129)对 MSC-EVs 的抗纤维化作用的贡献。我们的研究为基于使用 MSC 分泌组的富含囊泡部分的可能的抗纤维化治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/f1eaaca02857/12276_2023_1017_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/708c15579b96/12276_2023_1017_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/c5f10dd559df/12276_2023_1017_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/3320d7ed4037/12276_2023_1017_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/ea476162a18a/12276_2023_1017_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/ef656d834536/12276_2023_1017_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/f1eaaca02857/12276_2023_1017_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/708c15579b96/12276_2023_1017_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/c5f10dd559df/12276_2023_1017_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/3320d7ed4037/12276_2023_1017_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/ea476162a18a/12276_2023_1017_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/ef656d834536/12276_2023_1017_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ff/10393964/f1eaaca02857/12276_2023_1017_Fig6_HTML.jpg

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