Mesenchymal stem cell-derived small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission
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Updated: May 24, 2025
Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells
Published on: September 23, 2022
Yifei Chen1,2, Fuji Yang1,2, Yanjin Wang1,2
1Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, China.
Background:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by lipid accumulation in liver cells. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have great potential in repairing and regenerating liver diseases. However, it is still unclear whether MSC-sEV can inhibit hepatocyte lipid accumulation by regulating mitochondrial fission.
Methods:
We investigated the effects of MSC-sEV on mitochondrial fission and its potential mechanism in lipotoxic hepatocytes and high-fat diet (HFD)-induced MASLD mice.
Results:
We found that MSC-sEV can effectively inhibit the expression of the Dynamin-related protein 1 (DRP1), thereby reducing mitochondrial fission, mitochondrial damage, and lipid deposition in lipotoxic hepatocytes and livers of HFD-induced MASLD in mice. Further mechanistic studies revealed that RING finger protein 31 (RNF31) played a crucial role in mediating the inhibitory effect of MSC-sEV on DRP1 and mitochondrial fission. RNF31 can suppress DRP1 expression and mitochondrial fission, thereby improving mitochondrial dysfunction and reducing hepatocyte lipid deposition. These findings suggest that MSC-sEV may downregulate hepatocyte DRP1-mediated mitochondrial fission by transporting RNF31, ultimately inhibiting hepatocyte lipid accumulation.
Conclusions:
The insights from this study provide a new perspective on the mechanism of MSC-sEV in reducing lipid accumulation and offer a potential therapeutic target by targeting DRP1 to inhibit hepatocyte steatosis and the progression of MASLD.
