Collagen regulates the ability of endothelial progenitor cells to protect hypoxic myocardium through a mechanism involving miR‐377/VE‐PTP axis

Abstract

The possibility to employ stem/progenitor cells in the cardiovascular remodelling after myocardial infarction is one of the main queries of regenerative medicine. To investigate whether endothelial progenitor cells (EPCs) participate in the restoration of hypoxia‐affected myocardium, we used a co‐culture model that allowed the intimate interaction between EPCs and myocardial slices, mimicking stem cell transplantation into the ischaemic heart. On this model, we showed that EPCs engrafted to some extent and only transiently survived into the host tissue, yet produced visible protective effects, in terms of angiogenesis and protection against apoptosis and identified miR‐377‐VE‐PTP axis as being involved in the protective effects of EPCs in hypoxic myocardium. We also showed that collagen, the main component of the myocardial scar, was important for these protective effects by preserving VE‐PTP levels, which were otherwise diminished by miR‐377. By this, a good face of the scar is revealed, which was so far perceived as having only detrimental impact on the exogenously delivered stem/progenitor cells by affecting not only the engraftment, but also the general protective effects of stem cells.

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

“…The EPCs derived from human cord blood (human cord blood endothelial colony-forming cells or hCB-ECFCs) show much greater proliferative and angiogenic abilities compared with EPCs isolated from human peripheral blood (hPB-ECFCs) ( Peters, 2018 ). Until now, EPCs have been used for vascularizing common scaffolds such as decellularized scaffolds ( Guo et al, 2018 ), Poly-Ethylene Glycol Hydrogel ( Peters et al, 2016 ), and Matrigel ( Iqbal et al, 2017 ; Rosca et al, 2018 ). With all the controversies over the EPCs and their applications, they show promising potentials for scaffold vascularization ( Peters, 2018 ).…”

MicroRNA-326-5p enhances therapeutic potential of endothelial progenitor cells for myocardial infarction

“…Finally, EPCs differentiate into mature endothelial cells and initiate the repair process of neovascularization [9]. Therefore, direct transplantation of EPCs into the ischemic myocardium has been conducted and exhibited cardiac protective effects, including augmenting neovascularization, decreasing inflammatory apoptosis, and improving cardiac function [4, 10].…”