Investigation of the Molecular Mechanisms of Mesenchymal Stem/Stromal cells' Differentiation

Postgraduate Thesis uoadl:2798928 138 Read counter

Unit:
Κατεύθυνση Εφαρμογές της Βιολογίας στην Ιατρική
Library of the School of Science
Deposit date:
2018-09-26
Year:
2018
Author:
Psaraki Antrea-Antriana
Supervisors info:
Μαρία Ρουμπελάκη, Επίκουρη Καθηγήτρια Αναπτυξιακής Βιολογίας, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Διερεύνηση των Μοριακών Μηχανισμών Διαφοροποίησης των Μεσεγχυματικών Βλαστικών/Στρωματικών Κυττάρων
Languages:
Greek
Translated title:
Investigation of the Molecular Mechanisms of Mesenchymal Stem/Stromal cells' Differentiation
Summary:
The field of Mesenchymal Stem/Stromal Cells (MSCs) is considered very important in Regenerative Medicine research for therapies of various diseases, including liver malfunctions. MSCs are characterized by the ability of differentiation into various cell types, can be easily isolated, rapidly expanded in vitro and exhibit low immunological responses. Therefore can be considered as an ideal source of cells for treatment of various diseases, such as Acute Liver Failure (ALF). Interestingly, MSCs can also act therapeutically by their secreted molecules and extracellular vesicles, improving potential therapeutic approaches for ALF. Recent studies from our group and others indicated Amniotic Fluid as an important source of MSCs without ethical considerations.
Initially, AF-MSCs were isolated during the second trimester of pregnancy and expanded and differentiated into Hepatic Progenitor Like Cells (HPL). Following their differentiation into HPL, secretome and exosomes were isolated from AF-MSCs and HPL cells respectively, aiming to study their potential therapeutic role in ALF animal model.
Furthermore, exosomes derived from AF-MSCs and HPL were characterized by Transmission Electronic Microscopy (TEM) and Western Immunoblotting. The size of exosomes derived from AF-MSCs and HPL was within the range of general exosomes’ sizes and both types of exosomes expressed the exosomal markers, Flotilin, TSG101 and Alix, concluding their successful isolation.
In addition, the biological role of AF-MSCs and HPL secretome and exosomes was further investigated in ALF mouse model. More specifically, oval cells from Rag-/- mice were cultured in Conditioned Medium (CM) and exosomes derived from AF-MSCs and HPL cells. AF-MSCs and HPL CM and/or exosomes were administered in vivo in ALF Rag-/- mice. It was shown that CM from AF-MSCs or HPL statistical significantly improved the hepatic failure phenotype. More importantly, exosomes derived from AF-MSCs and HPL cells exhibited a similar therapeutic effect, enhancing their critical role in treatment of liver diseases.
In conclusion, AF-MSCs are considered a significant therapeutic cell type for hepatic failure mainly due to their plasticity and their secreted molecules and vesicles. Consequently, CM as well as exosomes derived from AF-MSCs and HPL represent a promising, non-invasive therapeutic solution for ALF.
Main subject category:
Science
Keywords:
Mesenchymal Stem/Stromal cells, Amniotic Fluid, Hepatic Progenitor Like Cells, Exosomes
Index:
Yes
Number of index pages:
2
Contains images:
Yes
Number of references:
171
Number of pages:
84

ΔΙΠΛΩΜΑΤΙΚΗ ΕΡΓΑΣΙΑ ΨΑΡΑΚΗ ΑΝΤΡΕΑ-ΑΝΤΡΙΑΝΑ, Διερεύνηση των Μοριακών Μηχανισμών Διαφοροποίησης των Μεσεγχυματικών ΒλαστικώνΣτρωματικών Κυττάρων 2018.pdf
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