Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells

• Published in: Journal of controlled release Vol. 338; pp. 505 - 526
• Main Authors: D'Souza, Anisha, Burch, Amelia, Dave, Kandarp M., Sreeram, Aravind, Reynolds, Michael J., Dobbins, Duncan X., Kamte, Yashika S., Zhao, Wanzhu, Sabatelle, Courtney, Joy, Gina M., Soman, Vishal, Chandran, Uma R., Shiva, Sruti S., Quillinan, Nidia, Herson, Paco S., Manickam, Devika S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-10-2021
• Subjects: Animals; BBB protection; Brain; Cell-Derived Microparticles; Endothelial Cells - metabolism; Exosomes; Extracellular vesicles; Extracellular Vesicles - metabolism; Ischemic stroke; Mice; Microvesicles; Mitochondria; Mitochondrial function; Mitochondrial transfer; Mitochondrial transfer; Mitochondrial function; Extracellular vesicles; Microvesicles; Ischemic stroke; Exosomes; BBB protection
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2021.08.038

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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•Microvesicles transfer mitochondria to endothelial cells and brain slice neurons.•Mitochondrial transfer increased ATP in ischemic brain endothelial cells (BECs).•Transfer of microvesicles increased mitochondrial function in hypoxic BECs.•Transfer of exosomes did not affect mitochondrial function in hypoxic BECs.•Homotypic BEC-derived EVs result in greater ATP levels in the recipient BECs.