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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
Author(s) -
Asgari Taei Afsaneh,
Dargahi Leila,
Nasoohi Sanaz,
Hassanzadeh Gholamreza,
Kadivar Mehdi,
Farahmandfar Maryam
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29981
Subject(s) - medicine , mesenchymal stem cell , stroke (engine) , transplantation , ischemia , neural stem cell , stem cell , embryonic stem cell , neuroprotection , anesthesia , pathology , cardiology , biology , microbiology and biotechnology , mechanical engineering , biochemistry , gene , engineering
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.