Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

Overview

Journal J Control Release

Specialty Pharmacology

Date 2021 Aug 27

PMID 34450196

Citations 52

Authors

Anisha DSouza

Amelia Burch

Kandarp M Dave

Aravind Sreeram

Michael J Reynolds

Duncan X Dobbins

Yashika S Kamte

Wanzhu Zhao

Courtney Sabatelle

Gina M Joy

Vishal Soman

Uma R Chandran

Sruti S Shiva

Nidia Quillinan

Paco S Herson

Devika S Manickam

Affiliations

Soon will be listed here.

Abstract

We have demonstrated, for the first time that microvesicles, a sub-type of extracellular vesicles (EVs) derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. We have also demonstrated that transfer of microvesicles, the larger EV fraction, but not exosomes resulted in increased mitochondrial function in hypoxic endothelial cultures. Gene ontology and pathway enrichment analysis of EVs revealed a very high association to glycolysis-related processes. In comparison to heterotypic macrophage-derived EVs, BEC-derived EVs demonstrated a greater selectivity to transfer mitochondria and increase endothelial cell survival under ischemic conditions.

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