Mansoureh Barzegar1, Yuping Wang2, Randa S Eshaq1, J Winny Yun1, Christen J Boyer1, Sergio G Cananzi3, Luke A White1, Oleg Chernyshev4, Roger E Kelley4, Alireza Minagar4, Karen Y Stokes1, Xiao-Hong Lu5, Jonathan S Alexander6. 1. Molecular and Cellular Physiology, Medicine and Neurology, Ochsner-LSU Health Sciences Center-1501 Kings Highway, Shreveport, LA 71130-3932, USA. 2. Obstetrics and Gynecology and Medicine, Ochsner-LSU Health Sciences Center-Shreveport, LA 71130, USA. 3. Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA. 4. Neurology, Ochsner-LSU Health Sciences Center-Shreveport, LA 71130, USA. 5. Pharmacology and Neuroscience, Ochsner-LSU Health Sciences Center-Shreveport, LA 71130, USA. 6. Molecular and Cellular Physiology, Medicine and Neurology, Ochsner-LSU Health Sciences Center-1501 Kings Highway, Shreveport, LA 71130-3932, USA; Neurology, Ochsner-LSU Health Sciences Center-Shreveport, LA 71130, USA. Electronic address: jalexa@lsuhsc.edu.
Abstract
BACKGROUND: Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. METHODS: We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke 'transient middle cerebral artery occusion (MCAO)/reperfusion' mice model. FINDINGS: We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. INTERPRETATION: Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid "translation" of these cells into clinical trials in the near-term.
BACKGROUND: Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. METHODS: We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke 'transient middle cerebral artery occusion (MCAO)/reperfusion' mice model. FINDINGS: We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. INTERPRETATION: Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid "translation" of these cells into clinical trials in the near-term.
Authors: Mansoureh Barzegar; Shantel Vital; Karen Y Stokes; Yuping Wang; Jungmi Winny Yun; Luke A White; Oleg Chernyshev; Roger E Kelley; Jonathan S Alexander Journal: Stem Cells Date: 2021-06-22 Impact factor: 5.845