Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells

Anisha D'Souza; 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

doi:10.1016/j.jconrel.2021.08.038

Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells

J Control Release. 2021 Oct 10:338:505-526. doi: 10.1016/j.jconrel.2021.08.038. Epub 2021 Aug 24.

Authors

Anisha D'Souza¹, Amelia Burch², Kandarp M Dave¹, Aravind Sreeram³, Michael J Reynolds⁴, Duncan X Dobbins¹, Yashika S Kamte¹, Wanzhu Zhao¹, Courtney Sabatelle¹, Gina M Joy¹, Vishal Soman⁵, Uma R Chandran⁵, Sruti S Shiva⁶, Nidia Quillinan², Paco S Herson², Devika S Manickam⁷

Affiliations

¹ Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
² Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ College of William & Mary, Williamsburg, VA, USA.
⁴ Heart, Lung, Blood Vascular Institute, University of Pittsburgh Medical School, PA, USA.
⁵ Department of Biomedical Informatics, University of Pittsburgh Medical School, PA, USA.
⁶ 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.
⁷ Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA. Electronic address: soundaramanickd@duq.edu.

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.

Keywords: BBB protection; Exosomes; Extracellular vesicles; Ischemic stroke; Microvesicles; Mitochondrial function; Mitochondrial transfer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
Cell-Derived Microparticles*
Endothelial Cells / metabolism
Extracellular Vesicles* / metabolism
Mice
Mitochondria

Abstract

Publication types

MeSH terms

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