Human embryonic stem cell-derived mesenchymal stem cells ameliorate mitochondrial oxidative dysfunction in metabolic dysfunction-associated steatotic liver disease.
- 1Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
- 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea.
- 3Biomedical Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Abstract
Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease with significant clinical burden. This study investigated the therapeutic potential of embryonic stem cell-derived mesenchymal stem cells (ESC-MSCs) in cellular and murine models of MASLD.Methods
HepG2 cells were treated with palmitic acid (PA) and then co-cultured with ESC-MSCs. C57BL/6 mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) or a standard diet for 24 weeks. Either ESC-MSCs or vehicles were administered via tail vein injection at week 20. Lipid accumulation was assessed using Oil red O staining. Mitochondrial status was assessed using MitoTracker Red fluorescence, mtDNA content, reactive oxygen species (ROS), and antioxidant parameters.Results
ESC-MSC co-culture reduced PA-induced lipid accumulation, restored mitochondrial activity, decreased ROS, and increased superoxide dismutase (SOD) activity and glutathione redox balance. Expression of phosphorylated AMPK (p-AMPK), PGC1α, and PPARα was significantly upregulated. In CDAHFD-fed mice, ESC-MSC transplantation attenuated hepatic steatosis, restored mitochondrial DNA content, and reduced ROS accumulation with increased SOD activity and glutathione ratio. Hepatic expression of p-AMPK, PGC1α, and PPARα was also enhanced. These effects were abrogated by Compound C, an AMPK inhibitor. ESC-MSCs secreted hepatocyte growth factor (HGF), which activated AMPK, suggesting an HGF-AMPK axis may serve as a potential paracrine mechanism.Conclusion
ESC-MSCs ameliorated hepatic steatosis in MASLD models by restoring mitochondrial activity and reducing oxidative stress, possibly involving HGF-associated AMPK pathway modulation. These findings support the potential of ESC-MSC therapy for MASLD.
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BibTeX
@article{park2026human,
title = {{Human embryonic stem cell-derived mesenchymal stem cells ameliorate mitochondrial oxidative dysfunction in metabolic dysfunction-associated steatotic liver disease.}},
author = {Min Kyung Park and Yun Bin Lee and Se-Mi Jung and Yoo-Wook Kwon and Jung-Hwan Yoon},
journal = {Stem cells translational medicine},
year = {2026},
month = oct,
doi = {10.1093/stcltm/szag089},
url = {https://europepmc.org/article/MED/42958001},
note = {CC BY},
}
RIS
TY - JOUR
TI - Human embryonic stem cell-derived mesenchymal stem cells ameliorate mitochondrial oxidative dysfunction in metabolic dysfunction-associated steatotic liver disease.
AU - Min Kyung Park
AU - Yun Bin Lee
AU - Se-Mi Jung
AU - Yoo-Wook Kwon
AU - Jung-Hwan Yoon
PY - 2026
DA - 2026/10/01
JO - Stem cells translational medicine
DO - 10.1093/stcltm/szag089
UR - https://europepmc.org/article/MED/42958001
AB - Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease with significant clinical burden. This study investigated the therapeutic potential of embryonic stem cell-derived mesenchymal stem cells (ESC-MSCs) in cellular and murine models of MASLD.Methods HepG2 cells were treated with palmitic acid (PA) and then co-cultured with ESC-MSCs. C57BL/6 mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) or a standard diet for 24 weeks. Either ESC-MSCs or vehicles were administered via tail vein injection at week 20. Lipid accumulation was assessed using Oil red O staining. Mitochondrial status was assessed using MitoTracker Red fluorescence, mtDNA content, reactive oxygen species (ROS), and antioxidant parameters.Results ESC-MSC co-culture reduced PA-induced lipid accumulation, restored mitochondrial activity, decreased ROS, and increased superoxide dismutase (SOD) activity and glutathione redox balance. Expression of phosphorylated AMPK (p-AMPK), PGC1α, and PPARα was significantly upregulated. In CDAHFD-fed mice, ESC-MSC transplantation attenuated hepatic steatosis, restored mitochondrial DNA content, and reduced ROS accumulation with increased SOD activity and glutathione ratio. Hepatic expression of p-AMPK, PGC1α, and PPARα was also enhanced. These effects were abrogated by Compound C, an AMPK inhibitor. ESC-MSCs secreted hepatocyte growth factor (HGF), which activated AMPK, suggesting an HGF-AMPK axis may serve as a potential paracrine mechanism.Conclusion ESC-MSCs ameliorated hepatic steatosis in MASLD models by restoring mitochondrial activity and reducing oxidative stress, possibly involving HGF-associated AMPK pathway modulation. These findings support the potential of ESC-MSC therapy for MASLD.
SN - 2157-6564
SN - 2157-6580
ER -