Intranasal delivery of SDF-1α-preconditioned bone marrow mesenchymal cells improves remyelination in the cuprizone-induced mouse model of multiple sclerosis

Beigi Boroujeni, F. and Pasbakhsh, P. and Mortezaee, K. and Pirhajati, V. and Alizadeh, R. and Aryanpour, R. and Madadi, S. and Ragerdi Kashani, I. (2020) Intranasal delivery of SDF-1α-preconditioned bone marrow mesenchymal cells improves remyelination in the cuprizone-induced mouse model of multiple sclerosis. Cell Biology International, 44 (2). pp. 499-511.

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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

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: chemokine receptor CXCR4; cuprizone; glial fibrillary acidic protein; oligodendrocyte transcription factor 2; stromal cell derived factor 1alpha, animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; bone marrow cell; bone marrow mesenchymal cell; C57BL 6 mouse; cell surface; cell survival; clinical effectiveness; colon polyposis; controlled study; drug effect; drug efficacy; drug mechanism; drug response; immunofluorescence; in vitro study; male; mesenchyme cell; Morris water maze test; mouse; multiple sclerosis; nonhuman; protein expression; remyelinization; spatial learning; transmission electron microscopy; treatment outcome
Subjects: WH Hemic and Lymphatic Systems
QZ Pathology
Depositing User: eprints admin
Date Deposited: 05 Sep 2020 08:59
Last Modified: 05 Sep 2020 08:59

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