AORTIC ENDOTHELIAL CELL PROLIFERATION INDUCED BY EXOSOMES OBTAINED FROM iPSC UNDER THE ACTION OF VARIOUS MODULATORS
Background: Extracellular vesicles (also known as EVs), secreted naturally by all cells, are known to act as mediators for intercellular communication. Aim: The goal of our study was represented by the quantification of rat aortic endothelial cell proliferation in culture in the presence of pluripotent stem cells (iPSC), chemically-induced from rat aortic smooth muscle cells (in co-culture) or in the presence of exosomes obtained, as a supernatant, from the culture medium of the latter cells, in the presence of 0.5 µM trichostatin A, 1 µM 6-mercaptopurine, 2 µM triamterene and 2 µM metformin. Material and methods: We used flow cytometry to quantify cell proliferation, using a membrane-permeable, tetramethylrodamine-based cellular tracking agent, 48 hours after inclusion in the culture medium. Results: The best proliferation for aortic endothelial cells, in the presence of exosomes obtained from the culture supernatant of pluripotent stem cells, chemically-induced from vascular smooth muscle cells, was obtained when grew these latest cell types on 3D biosupports and treated with 2 µM metformin. Conclusions: It is suggested that epigenetic changes, genome stabilization, and, especially, reprogramming of energy metabolism, result in the release of exosomes from induced pluripotent stem cells that have the ability to significantly amplify aortic endothelial cell proliferation in culture.
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