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Intranasal Delivery of Sdf-1Α-Preconditioned Bone Marrow Mesenchymal Cells Improves Remyelination in the Cuprizone-Induced Mouse Model of Multiple Sclerosis Publisher Pubmed



Beigi Boroujeni F1 ; Pasbakhsh P1 ; Mortezaee K2 ; Pirhajati V3 ; Alizadeh R4 ; Aryanpour R5 ; Madadi S1 ; Ragerdi Kashani I1
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, Faculty of Medicine, Tehran University of Medical Science, Tehran, 1417653761, Iran
  2. 2. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
  3. 3. Neuroscience Research Center, Vice-Chancellor for Research and Technology, Iran University of Medical Science, Tehran, 1449614535, Iran
  4. 4. ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Tehran, 1445613131, Iran
  5. 5. Department of Anatomy, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, 7591741417, Iran

Source: Cell Biology International Published:2020


Abstract

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that leads to disability in middle-aged individuals. High rates of apoptosis and inappropriate homing are limitations for the application of stem cells in cell therapy. Preconditioning of bone marrow mesenchymal stem cells (BMSCs) with stromal cell-derived factor 1α (SDF-1α), also called C-X-C motif chemokine 12 (CXCL12), is an approach for improving the functional features of the cells. The aim of this study was to investigate the therapeutic efficacy of intranasal delivery of SDF-1α preconditioned BMSCs in the cuprizone-induced chronically demyelinated mice model. BMSCs were isolated, cultured, and preconditioned with SDF-1α. Then, intranasal delivery of the preconditioned cells was performed in the C57BL/6 mice receiving cuprizone for 12 weeks. Animals were killed at 30 days after cell delivery. SDF-1α preconditioning increased C-X-C chemokine receptor type 4 (CXCR4) expression on the surface of BMSCs, improved survival of the cells, and decreased their apoptosis in vitro. SDF-1α preconditioning also improved CXCL12 level within the brain, and enhanced spatial learning and memory (assessed by Morris water maze [MWM]), and myelination (assessed by Luxol fast blue [LFB] and transmission electron microscopy [TEM]). In addition, preconditioning of BMSCs with SDF-1α reduced the protein expressions of glial fibrillary acidic protein and ionized calcium-binding adapter molecule (Iba-1) and increased the expressions of oligodendrocyte lineage transcription factor-2 (Olig-2) and adenomatous polyposis coli (APC), evaluated by immunofluorescence. The results showed the efficacy of intranasal delivery of SDF-1α-preconditioned BMSCs for improving remyelination in the cuprizone model of MS. © 2019 International Federation for Cell Biology
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