Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis

Stem Cell Res Ther. 2025 Jan 7;16(1):4. doi: 10.1186/s13287-024-04013-7.

Abstract

Background: As cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood.

Methods and results: In this study, we utilized a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model to investigate the effects of MSC-EVs on AIH. We found that MSC-EVs provide significant protection against Con A-induced hepatitis in C57BL/6 male mice, with their effectiveness being critically dependent on the gut microbiota. MSC-EVs modulate the composition of the gut microbiota, particularly by increasing the abundance of norank_f__Muribaculaceae, and impact liver metabolic profiles, leading to significant amelioration of liver injury. The identification of Acetyl-DL-Valine as a protective metabolite underscores the therapeutic potential of targeting gut‒liver axis interactions in liver diseases.

Conclusion: Overall, our data demonstrate that MSC-EVs exhibit nanotherapeutic potential in Con A-induced hepatitis and provide new insights into the treatment of autoimmune hepatitis.

Keywords: Con A-induced hepatitis; Extracellular vesicles; Gut microbiota; Mesenchymal stromal cells.

MeSH terms

  • Animals
  • Concanavalin A*
  • Disease Models, Animal
  • Extracellular Vesicles* / metabolism
  • Gastrointestinal Microbiome / drug effects
  • Hepatitis, Autoimmune* / drug therapy
  • Hepatitis, Autoimmune* / metabolism
  • Hepatitis, Autoimmune* / pathology
  • Hepatitis, Autoimmune* / therapy
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Inbred C57BL*

Substances

  • Concanavalin A