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The Conditioned Medium of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Alleviates Neurological Deficits and Improves Synaptic Recovery in Experimental Stroke Publisher Pubmed



Asgari Taei A1 ; Dargahi L2 ; Nasoohi S3 ; Hassanzadeh G1, 4, 5 ; Kadivar M6 ; Farahmandfar M1, 7
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Authors Affiliations
  1. 1. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
  6. 6. Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
  7. 7. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Cellular Physiology Published:2021


Abstract

The transplantation of mesenchymal stem cells (MSCs) is of main approaches in regenerative therapy for stroke. Due to the potential tumorigenicity and low survival rate of transplanted cells, focuses have been shifted from cell replacement to their paracrine effects. Therefore, stem cell-conditioned medium (CM) therapy has emerged as an alternative candidate. Here, we investigated the effect of CM derived from human embryonic MSCs on experimental ischemic stroke. Wistar rats underwent ischemic stroke by the right middle cerebral artery occlusion (MCAO). CM was infused either one time (1 hr post-MCAO) or three times (1, 24, and 48 hr post-MCAO) through guide cannula into the left lateral ventricle. Neurological functions were evaluated using Bederson's test and modified Neurological Severity Score on Days 1, 3, and 7 following MCAO. Infarction volumes and cerebral edema were measured on Days 3 and 7. growth-associated protein-43, synaptophysin, cAMP response element-binding protein, and phosphorylated-cAMP response element-binding protein levels were also assessed in peri-ischemic cortical tissue on Day 7 postsurgery. Our results indicated that three times injections of CM could significantly reduce body weight loss, mortality rate, infarct volumes, cerebral edema, and improve neurological deficits in MCAO rats. Moreover, three injections of CM could restore decreased levels of synaptic markers in MCAO rats up to its normal levels observed in the sham group. Our data suggest that using the CM obtained from embryonic stem cells–MSCs could be a potent therapeutic approach to attenuate cerebral ischemia insults which may be partly mediated through modulation of synaptic plasticity. © 2020 Wiley Periodicals LLC
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Maryam Farahmandfar (4)
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