iScience (Nov 2023)

MFGE-8 identified in fetal mesenchymal-stromal-cell-derived exosomes ameliorates acute hepatic failure pathology

  • Adriana Psaraki,
  • Dimitra Zagoura,
  • Lydia Ntari,
  • Manousos Makridakis,
  • Christina Nikokiraki,
  • Ourania Trohatou,
  • Konstantina Georgila,
  • Christos Karakostas,
  • Ioanna Angelioudaki,
  • Anastasios G. Kriebardis,
  • Roberto Gramignioli,
  • Stratigoula Sakellariou,
  • Maria Xilouri,
  • Aristides G. Eliopoulos,
  • Antonia Vlahou,
  • Maria G. Roubelakis

Journal volume & issue
Vol. 26, no. 11
p. 108100

Abstract

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Summary: Liver transplantation is the gold-standard therapy for acute hepatic failure (AHF) with limitations related to organ shortage and life-long immunosuppressive therapy. Cell therapy emerges as a promising alternative to transplantation. We have previously shown that IL-10 and Annexin-A1 released by amniotic fluid human mesenchymal stromal cells (AF-MSCs) and their hepatocyte progenitor-like (HPL) or hepatocyte-like (HPL) cells induce liver repair and downregulate systemic inflammation in a CCl4-AHF mouse model. Herein, we demonstrate that exosomes (EXO) derived from these cells improve liver phenotype in CCl4-induced mice and promote oval cell proliferation. LC-MS/MS proteomic analysis identified MEFG-8 in EXO cargo that facilitates rescue of AHF by suppressing PI3K signaling. Administration of recombinant MFGE-8 protein also reduced liver damage in CCl4-induced mice. Clinically, MEFG-8 expression was decreased in liver biopsies from AHF patients. Collectively, our study provides proof-of-concept for an innovative, cell-free, less immunogenic, and non-toxic alternative strategy for AHF.

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