Anti-liver fibrotic effects of small extracellular vesicle microRNAs from human umbilical cord-derived mesenchymal stem cells and their differentiated hepatocyte-like cells

被引:1
作者
Choi, Min-Seok [1 ]
Hong, Jae-Sang [1 ,2 ]
Lee, Do-Hoon [1 ,3 ]
Jang, Yu Jin [1 ,4 ]
Kim, Jong-Hoon [1 ]
Lee, Young Sik [1 ]
机构
[1] Korea Univ, Coll Life Sci & Biotechnol, Seoul 02841, South Korea
[2] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA
[3] Seegene Inc, Seoul 05548, South Korea
[4] I Peace Inc, Peace Lab Calif, Cell & Gene Therapy Mfg, Palo Alto, CA 94303 USA
基金
新加坡国家研究基金会;
关键词
Hepatic stellate cell; Liver fibrosis; Mesenchymal stem cell; MicroRNA; Small extracellular vesicle; HEPATIC STELLATE CELLS; FIBROSIS; MIRNAS;
D O I
10.1007/s10529-025-03579-3
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Objective The aim of this study is to identify therapeutic cargos within mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) for the treatment of liver fibrosis, a condition that poses significant health risks. Results sEVs from human umbilical cord-derived MSCs (UCMSCs) and their differentiated hepatocyte-like cells (hpUCMSCs) were found to alleviate liver fibrosis in mouse models, reduce fibrogenic gene expression in the liver, and inhibit hepatic stellate cell (HSC) activation, a central driver of liver fibrosis, in vitro. Deep sequencing identified differentially abundant microRNAs (miRNAs) (high-abundance: 57, low-abundance: 22) in both UCMSC- and hpUCMSC-derived sEVs, compared to HeLa cell-derived sEVs, which lack anti-liver fibrotic activity. Functional enrichment analysis of the high-abundance sEV miRNA targets revealed their involvement in transcriptional regulation, apoptosis, and cancer-related pathways, all of which are linked to liver fibrosis and hepatocellular carcinoma. Notably, many of the top 10 most abundant miRNAs reduced pro-fibrotic marker levels in activated HSCs in vitro. Conclusion The therapeutic potential of the high-abundance miRNAs shared by UCMSC- and hpUCMSC-derived sEVs in treating liver fibrosis is highlighted.
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页数:14
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