Endothelial Progenitor Cell-Derived Microvesicles Promote Angiogenesis in Rat Brain Microvascular Endothelial Cells In vitro

Abstract

Brain microvascular endothelial cells (BMECs) are a major component of the blood-brain barrier that maintains brain homeostasis. Preserving and restoring the normal biological functions of BMECs can reverse or reduce brain injury. Endothelial progenitor cells (EPCs) may promote brain vascular remodeling and restore normal endothelial function. As a novel vehicle for cell-cell communication, microvesicles (MVs) have varied biological functions. The present study investigated the biological effects of EPC-derived MVs (EPC-MVs) on BMECs in vitro. We isolated MVs from the supernatant of EPCs in a serum-depleted medium. BMECs were cultured alone or in the presence of EPC-MVs. BMEC viability and proliferation were evaluated with the Cell Counting Kit-8 and by flow cytometry, and the proangiogenic effect of EPC-MVs on BMECs was assessed with the transwell migration, wound healing, and tube formation assays. Our results showed that EPC-derived MVs labeled with DiI were internalized by cultured BMECs; this enhanced BMEC viability and promoted their proliferation. EPC-MVs also stimulated migration and tube formation in BMECs. These results demonstrate that EPC-derived MVs exert a proangiogenic effect on BMECs, which has potential applications in cell-free therapy for brain injury.

Protective effects of endothelial progenitor cell microvesicles on Ang II‑induced rat kidney cell injury

“…EPCs effectively protect renal function in CKD ( 40 ) and serve a major role in maintaining vascular integrity and repairing endothelial injury ( 15 ), as well as reduce vascular leakage, improve organ function and increase survival rate in sepsis ( 41 ). Accumulating evidence suggests that EPCs may exert a protective role via the secretion of MVs ( 37 , 42 , 43 ).…”

Cell-Derived Exosomes as Therapeutic Strategies and Exosome-Derived microRNAs as Biomarkers for Traumatic Brain Injury

“…It is well known that brain microvascular endothelial cells (BMECs) are one of the major components of BBB that maintain brain homeostasis. Endothelial progenitor cell-derived microvesicles have been reported to promote angiogenesis in rat BMECs in vitro [ 113 ]. In an experimental mice model, plasma endothelial cell-derived microvesicles (PECD-MVs) contained elevated levels of occludin, leading to vascular remodeling of BBB [ 108 ].…”

Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update

“…When ICH occurs, the BBB structure is damaged, which can be improved by EPCs and their secreted external vesicles [ 64 , 91 , 92 , 151 ]. Zeng et al [ 152 ] found that EVs secreted by mouse EPCs could promote proliferation, migration, and tube formation of BMECs. In another study on human cells, Loiola Azevedo et al [ 151 ] found that human EPC-secretome decreased the permeability of confluent monolayers of endothelial cells by increasing the expression of occludin, VE-cadherin, and ZO-1.…”