2. Academic Validation
  3. Mesenchymal stem cell-derived small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission

Mesenchymal stem cell-derived small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission

  • Stem Cell Res Ther. 2025 Mar 5;16(1):116. doi: 10.1186/s13287-025-04228-2.
Yifei Chen # 1 2,  Fuji Yang # 1 2,  Yanjin Wang 1 2,  Yujie Shi 1 2,  Likang Liu 1 2,  Wei Luo 3 4,  Jing Zhou 3 4,  Yongmin Yan 5 6 7
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, China.
  • 2 Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
  • 3 Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Changzhou, 213017, China.
  • 4 Changzhou Key Laboratory of Exosome Foundation and Transformation Application, Wujin Hospital Affiliated with Jiangsu University (Wujin Clinical College of Xuzhou Medical University, Changzhou, 213017, China.
  • 5 Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, China. yym@wjrmyy.cn.
  • 6 Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Changzhou, 213017, China. yym@wjrmyy.cn.
  • 7 Changzhou Key Laboratory of Exosome Foundation and Transformation Application, Wujin Hospital Affiliated with Jiangsu University (Wujin Clinical College of Xuzhou Medical University, Changzhou, 213017, China. yym@wjrmyy.cn.
  • # Contributed equally.
PMID: 40045380 DOI: 10.1186/s13287-025-04228-2
Abstract

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.

Keywords

DRP1; MASLD; MSC; Mitochondrial fission; Small extracellular vesicles.

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