Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells

DOI

10.1016/j.jconrel.2021.08.038

Anisha D'Souza, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Amelia Burch, Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kandarp M. Dave, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Aravind Sreeram, College of William & Mary, Williamsburg, VA, USA.
Michael J. Reynolds, Heart, Lung, Blood Vascular Institute, University of Pittsburgh Medical School, PA, USA.
Duncan X. Dobbins, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Yashika S. Kamte, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Wanzhu Zhao, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Courtney Sabatelle, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Gina M. Joy, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
Vishal Soman, Department of Biomedical Informatics, University of Pittsburgh Medical School, PA, USA.
Uma R. Chandran, Department of Biomedical Informatics, University of Pittsburgh Medical School, PA, USA.
Sruti S. Shiva, Heart, Lung, Blood Vascular Institute, University of Pittsburgh Medical School, PA, USA; Department of Pharmacology & Chemical Biology, Pittsburgh Heart Lung Blood Vascular Institute, University of Pittsburgh Medical School, PA, USA.
Nidia Quillinan, Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Paco S. Herson, Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Devika S. Manickam, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA. Electronic address: soundaramanickd@duq.edu.

Document Type

Journal Article

Publication Date

10-10-2021

Publication Title

Journal of controlled release : official journal of the Controlled Release Society

Volume

338

First Page

505

Last Page

526

Keywords

BBB protection, Exosomes, Extracellular vesicles, Ischemic stroke, Microvesicles, Mitochondrial function, Mitochondrial transfer

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.

Open Access

OA

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