title: Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.
abstract: Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sabbaghziarani
authors.affiliation: Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
authors.forename: Keywan
authors.initials: K
authors.lastname: Mortezaee
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran.
authors.forename: Iraj Ragerdi
authors.initials: IR
authors.lastname: Kashani
authors.affiliation: Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansooreh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Gynecology and Obstetrics, Roointan Arash women's Health Research and Education Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Moini
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Ataeinejad
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran. hassanzadeh@tums.ac.ir.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000628:therapy*; D020547:Lateral Ventricles / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D064231:Nestin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049230:Retinoid X Receptor beta / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D020521:Stroke / Q000378:metabolism / Q000628:therapy*; D014212:Tretinoin / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000627:therapeutic use*; D059631:Wharton Jelly
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D064231:Nestin; D049230:Retinoid X Receptor beta; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat; D014284:Triiodothyronine; D014212:Tretinoin
keywords: Ischemia; Neurogenesis; Retinoic acid; Triiodothyronine; Wharton’s jelly mesenchymal stem cells