Min-Seok Choi, Jae-Sang Hong, Do-Hoon Lee, Yu Jin Jang, Jong-Hoon Kim, Young Sik Lee
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Anti-liver fibrotic effects of small extracellular vesicle microRNAs from human umbilical cord-derived mesenchymal stem cells and their differentiated hepatocyte-like cells.
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.
期刊介绍：
Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them.
All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included.
Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields.
The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories.
Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.
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