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Extracellular Vesicles Derived From Human Umbilical Cord Perivascular Cells Improve Functional Recovery in Brain Ischemic Rat Via the Inhibition of Apoptosis Brain Ischemic Rat Via the Inhibition of Apoptosis Publisher Pubmed



Seifali E1 ; Hassanzadeh G1 ; Mahdavipour M1 ; Mortezaee K2 ; Moini A3, 4, 5 ; Satarian L6 ; Shekari F7 ; Nazari A7 ; Movassaghi S8 ; Akbari M1
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
  3. 3. Department of Gynecology and Obstetrics, School of Medicine, Tehran University of Medical Science, Tehran, Iran
  4. 4. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  5. 5. Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Brain and Cognitive Science, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  7. 7. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  8. 8. Department of Anatomy and cognitive neuroscience, School of Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

Source: Iranian Biomedical Journal Published:2020


Abstract

Background: Ischemic stroke, as a health problem caused by the reduced blood supply to the brain, can lead to the neuronal death. The number of reliable therapies for stroke is limited. MSCs exhibit therapeutic achievement. A major limitation of MSC application in cell therapy is the short survival span. MSCs affect target tissues through the secretion of many paracrine agents including EVs. This study aimed to investigate the effect of HUCPVCs-derived EVs on apoptosis, functional recovery, and neuroprotection. Methods: Ischemia was induced by MCAO in male Wistar rats. Animals were classified into sham, MCAO, MCAO + HUCPVC, and MCAO + EV groups. Treatments began at two hours after ischemia. Expressions of apoptotic-related proteins (BAX/BCl-2 and caspase-3 and -9), the amount of TUNEL-positive cells, neuronal density (MAP2), and dead neurons (Nissl staining) were assessed on day seven post MCAO. Results: Administration of EVs improved the sensorimotor function (p < 0.001) and reduced the apoptotic rate of Bax/Bcl-2 ratio (p < 0.001), as well as caspases and TUNEL-positive cells (p < 0.001) in comparison to the MCAO group. EV treatment also reduced the number of dead neurons and increased the number of MAP2+ cells in the IBZ (p < 0.001), as compared to the MCAO group. Conclusion: Our findings showed that HUCPVCs-derived EVs are more effective than their mother’s cells in improving neural function, possibly via the regulation of apoptosis in the ischemic rats. The strategy of cell-free extracts is, thus, helpful in removing the predicaments surrounding cell therapy in targeting brain diseases. © 2020, Pasteur Institute of Iran. All rights reserved.
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