Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Psaraki Antrea-Antriana
Dissertation committee:
Ρουμπελάκη Μαρία , Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γαζούλη Μαρία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ηλιόπουλος Αριστείδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σακελλαρίου Στρατηγούλα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ξυλούρη Μαρία, Ερευνήτρια Γ, ΙΙΒΕΑΑ
Τρουγκάκος Ιωάννης, Καθηγητής, Τμήμα Βιολογίας, ΕΚΠΑ
Πολίτης Παναγιώτης, Ερευνητής Α, ΙΙΒΕΑΑ
Original Title:
Καινοτόμος θεραπευτική προσέγγιση βασισμένη στο εκκρίτωμα των μεσεγχυματικών βλαστικών/στρωματικών κυττάρων για ηπατικές νόσους
Translated title:
An innovative therapeutic approach based on the secretome of mesenchymal stem/stromal cells for liver diseases
Summary:
BACKGROUND & AIMS: Acute hepatic failure (AHF) is a rapid deterioration of liver function with a high mortality rate. Liver transplantation is the gold standard therapy for AHF with limitations related to donor organ shortage and life-long immunosuppressive therapy. APPROACH & RESULTS: Data presented here present a new concept in AHF therapy based on the secreted exosomes by amniotic fluid mesenchymal stem/stromal Cells (AF-MSCs) and their hepatocyte progenitor-like (HPL) cells or hepatocyte-Like (HPL) in an AHF mouse model. Our previous studies have shown that AF-MSCs and HPL cells could induce liver repair and down-regulate the systemic inflammation in female Rag-/- CCL4- mice, by secretion of cytokines, such as IL-10 and Annexin A1. In the present study, we demonstrate the therapeutic effects of isolated exosomes in ex vivo and in vivo experimental models of AHF disease. More specifically, exosomes derived from the three cell types improved liver phenotype in CCL4-mice and promoted oval cell proliferation. To determine the molecular mediators of the therapeutic potential of exosomes in AHF, the proteomic profiles from AF-MSC-EXO, HPL-EXO and HL–EXO were further analyzed with high resolution LC-MS/MS. Interestingly, MFGE-8 protein and PI3K pathway were selected for further functional analysis and validation in the context of AHF. In addition, analysis of human biopsies from AHF patients, revealed lower expression of MFGE-8 compared to samples from control patients. Conclusions: The data presented herein lead to an innovative, cell free, non-invasive, less immunogenic and non-toxic alternative strategy to AHF treatment, providing new mechanistic information for future, precise exosome-based liver therapies.
Main subject category:
Health Sciences
Keywords:
Mesenchymal stem cells, Acute hepatic failure, exosomes, Mfge-8
Number of references:
266
File:
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Psaraki_Antrea_Antriana_PhD.pdf
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