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

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 am...

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Detalles Bibliográficos
Autores principales: Psaraki, Adriana, Zagoura, Dimitra, Ntari, Lydia, Makridakis, Manousos, Nikokiraki, Christina, Trohatou, Ourania, Georgila, Konstantina, Karakostas, Christos, Angelioudaki, Ioanna, Kriebardis, Anastasios G., Gramignioli, Roberto, Sakellariou, Stratigoula, Xilouri, Maria, Eliopoulos, Aristides G., Vlahou, Antonia, Roubelakis, Maria G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616317/
https://www.ncbi.nlm.nih.gov/pubmed/37915594
http://dx.doi.org/10.1016/j.isci.2023.108100
Descripción
Sumario: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.