Cargo proteins in extracellular vesicles: potential for novel therapeutics in non-alcoholic steatohepatitis

J Nanobiotechnology. 2021 Nov 17;19(1):372. doi: 10.1186/s12951-021-01120-y.

Abstract

Background: Extracellular vesicles (EVs) are recognized as novel cell-free therapeutics. Non-alcoholic steatohepatitis (NASH) remains a critical health problem. Herein, we show that EVs from pan peroxisome proliferator-activated receptor agonist-primed induced mesenchymal stem cell (pan PPAR-iMSC-EVs) has unique cargo protein signatures, and demonstrate its therapeutic function in NASH.

Results: A unique protein signatures were identified in pan PPAR-iMSC-EVs against those from non-stimulated iMSC-EVs. NASH mice receiving pan PPAR-iMSC-EVs showed reduced steatotic changes and ameliorated ER stress and mitochondiral oxidative stress induced by inflammation. Moreover, pan PPAR-iMSC-EVs promoted liver regeneration via inhibiting apoptosis and enhancing proliferation.

Conclusions: We conclude that our strategy for enriching unique cargo proteins in EVs may facilitate the development of novel therapeutic option for NASH.

Keywords: Extracellular vesicles; Induced mesenchymal stem cells; Inflammation; Non-alcoholic steatohepatitis; Regeneration; Steatosis.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Extracellular Vesicles* / chemistry
  • Extracellular Vesicles* / metabolism
  • Inflammation / metabolism
  • Liver* / chemistry
  • Liver* / metabolism
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Peroxisome Proliferator-Activated Receptors / metabolism

Substances

  • Peroxisome Proliferator-Activated Receptors