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

Autor: Psaraki A; 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., Zagoura D; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Ntari L; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Makridakis M; Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece., Nikokiraki C; 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., Trohatou O; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Georgila K; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Karakostas C; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Angelioudaki I; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Kriebardis AG; 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., Gramignioli R; 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., Sakellariou S; First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Xilouri M; Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece., Eliopoulos AG; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece., Vlahou A; Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece., Roubelakis MG; 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.
Jazyk: angličtina
Zdroj: IScience [iScience] 2023 Sep 30; Vol. 26 (11), pp. 108100. Date of Electronic Publication: 2023 Sep 30 (Print Publication: 2023).
DOI: 10.1016/j.isci.2023.108100
Abstrakt: 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 CCl 4 -AHF mouse model. Herein, we demonstrate that exosomes (EXO) derived from these cells improve liver phenotype in CCl 4 -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 CCl 4 -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.
Competing Interests: None declared.
(© 2023 The Authors.)
Databáze: MEDLINE
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