Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells

JOURNAL OF CONTROLLED RELEASE

卷:338

Article

D'Souza, Anisha^1,2,9  Burch, Amelia³  Dave, Kandarp M.^1,2  Sreeram, Aravind⁴  Reynolds, Michael J.⁵  Dobbins, Duncan X.^1,2  Kamte, Yashika S.^1,2  Zhao, Wanzhu^1,2  Sabatelle, Courtney^1,2  Joy, Gina M.^1,2  Soman, Vishal⁷  Chandran, Uma R.⁷  Shiva, Sruti S.^5,6  Quillinan, Nidia³  Herson, Paco S.^3,8  Manickam, Devika S.^1,2 

[1] Duquesne Univ, Grad Sch Pharmaceut Sci, Pittsburgh, PA USA

[2] Duquesne Univ, Sch Pharm, Pittsburgh, PA USA

[3] Univ Colorado, Dept Anesthesiol, Sch Med, Anschutz Med Campus, Aurora, CO USA

[4] Coll William & Mary, Williamsburg, VA USA

[5] Univ Pittsburgh, Sch Med, Heart Lung Blood Vasc Inst, Pittsburgh, PA 15260 USA

[6] Univ Pittsburgh, Pittsburgh Heart Lung Blood Vasc Inst, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15260 USA

[7] Univ Pittsburgh, Dept Biomed Informat, Sch Med, Pittsburgh, PA 15260 USA

[8] Ohio State Univ, Sch Med, Cerebrovasc Res Inst, Columbus, OH 43210 USA

[9] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA

关键词: Extracellular vesicles;    Microvesicles;    Exosomes;    Mitochondrial transfer;    Mitochondrial function;    BBB protection;    Ischemic stroke;   

DOI  :  10.1016/j.jconrel.2021.08.038

来源: Elsevier

【 摘 要 】

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 glycolysisrelated 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.

【 授权许可】

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