ArticleJournal of biosciences2026
Preconditioned umbilical-cord mesenchymal stem-cell exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miRNA signaling rather than HGF signaling.
Article in Journal of biosciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Biliary atresia (BA) is a prominent cause of liver cirrhosis in pediatric patients with a high pediatric end-stage liver disease (PELD) score and a Laennec score of 4 at the Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. Bile duct-ligated rat models have been used to mimic the clinical condition of BA partially. This study aims to evaluate the potential miRNAs of preconditioned umbilical-cord mesenchymal stem-cell exosomes (UC-MSC-exosomes) in comparison with the combined exosomes-HGF effect on liver histology, liver function, and hepatocyte-signaling in bile duct-ligated rats. Characterization of preconditioned UC-MSC-exosomes fulfilled the ISEV 2018 criteria. Liver histology showed trends of hepatocytes, inflammatory cells, and oval cell numbers returning to slightly below normal levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination, with no statistically significant difference. A significant difference in bile duct proliferation post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination was observed when compared with the control. Trends towards lower deposition of collagen around the porta area and total area fractions post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination showed no statistically significant difference; however, there was a slightly lower total collagen area fraction in the exosomes-HGF combination group. Functional hepatocyte preservation was indicated by increased albumin expression and partially improved CYP3A4 levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination. There was also a different trend in functional hepatocyte biochemical markers, SGOT (AST) and SGPT (ALT), between preconditioned UC-MSC-exosomes and the exosomes-HGF combination. NanoString microarray analysis of liver tissue and bioinformatics analysis were done to investigate in-depth hepatocyte signaling. miRNA profiling of the liver from preconditioned UC-MSC-exosomes identified the upregulation of hsa-miR-1-3p and hsa-miR-372-3p, which inhibit key signaling pathways, e.g., MAPK, PI3K-AKT, and NF-κB, and the downregulation of hsa-miR-520a-3p, which promotes hepatocyte proliferation and survival. miRNA profiles of the liver from the exosomes-HGF combination identified five different miRNA expressions (upregulated hsa-miR-144-3p, hsa-let7-5p, hsa-let7a-5p, hsa-let7e-5p, and hsa-miR-32-5p) and shared only one similar miR with the exosomes-treated liver (downregulated hsa-520a-3p). These miR differences contribute to the hepatocyte signaling in the exosomes-HGF combination group. Preconditioned UC-MSC-exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miR-mediated signaling rather than HGF signaling.
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