Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy.

Autor: Dave KM; Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America., Venna VR; Department of Neurology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States of America., Rao KS; Pittsburgh Heart Lung Blood Vascular Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America., Stolz DB; Center for Biologic Imaging, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America., Brady B; Human Biology, South Dakota State University, Brookings, SD, United States of America., Quaicoe VA; Department of Neurology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States of America., Maniskas ME; Department of Neurology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States of America., Hildebrand EE; Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America; Department of Psychology, Westminster College, New Wilmington, PA, United States of America., Green D; Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America., Chen M; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States of America., Milosevic J; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States of America; Captis Diagnostics Inc, Pittsburgh, PA, United States of America., Zheng SY; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States of America., Shiva SS; Pittsburgh Heart Lung Blood Vascular Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America; Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America., McCullough LD; Department of Neurology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States of America., S Manickam D; Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America. Electronic address: soundaramanickd@duq.edu.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Sep; Vol. 373, pp. 803-822. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1016/j.jconrel.2024.07.065
Abstrakt: Ischemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells (BECs) results in long-term neurological dysfunction post-stroke. We previously reported data from a pilot study where intravenous administration of human BEC (hBEC)-derived mitochondria-containing extracellular vesicles (EVs) showed a potential efficacy signal in a mouse middle cerebral artery occlusion (MCAo) model of stroke. We hypothesized that EVs harvested from donor species homologous to the recipient species (e.g., mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC (mBEC)-derived EVs may improve post-stroke outcomes in MCAo mice. We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs) vs. cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs or vice versa). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in MCAo mice support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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