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. 2021 Oct 8;22(19):10890. doi: 10.3390/ijms221910890

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Major factors affecting adipose-derived mesenchymal stem/stromal cell (ASC) differentiation into endothelial cells (ECs). Fibroblast growth factor 2 (FGF-2) activates the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, leading to the phosphorylation of forkhead box protein O1 (FOXO1), which decreases its transcriptional activity. As a result, the levels of miR-145 decrease and the levels of its downstream target V-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1) increase, which upregulate the transcription of EC-related genes. VEGF, on the other hand, activates ERK signaling pathway via VEGFR2 activation, leading to upregulation of EC genes, while MMP2 and -14 induce VEGFR2 cleavage and decrease in downstream signaling. Additionally, environmental factors such as shear force, hypoxia, EC priming of ASCs and 3D culture conditions enhance endothelial differentiation of ASCs.