Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece; Cell and Gene Therapy Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
Dimitra Zagoura
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Lydia Ntari
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Manousos Makridakis
Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
Christina Nikokiraki
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece; Cell and Gene Therapy Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
Ourania Trohatou
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Konstantina Georgila
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Christos Karakostas
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Ioanna Angelioudaki
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Anastasios G. Kriebardis
Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str, 12243 Egaleo, Greece
Roberto Gramignioli
Clinical Pathology and Cancer Diagnosis Unit, Karolinska Institute, 141 57 Huddinge, Sweden; Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, 171 77 Stockholm, Sweden
Stratigoula Sakellariou
First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Maria Xilouri
Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
Aristides G. Eliopoulos
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Antonia Vlahou
Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece
Maria G. Roubelakis
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece; Cell and Gene Therapy Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece; Corresponding author
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.