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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. [ABSTRACT FROM AUTHOR]

Background: Nowadays, transplantation of Bone marrow-derived Mesenchymal Stromal Cells (BMSCs) is currently an important alternative therapy for patient's type 1 diabetes mellitus. But a number of critical obstacles lie ahead of this new strategy including reducing stem cell homing to the damaged tissue due to oxidative stress. The purpose of the present study was to investigate whether preconditioning of BMSCs with SDF-1 could enhance their homing to the pancreas and promote regeneration of the pancreatic β cells after being intravenously injected. Methods: Mice BMSCs were isolated and expanded. Cell proliferation was assayed by MTT Assay. Preconditioning was performed with 10 ng/ml SDF-1α for 24 hr. Male NMRI mice were injected with high-dose STZ (150 mg/kg). The preconditioned or un- preconditioned BMSCs at a dose of 1x106 cells were infused via the tail vein. Blood and pancreatic tissue samples were taken from all mice for flow cytometry, biochemical and histological studies. Results: Proliferation and homing of BMSCs to the pancreas were significantly increased in the BMSCs with SDF-1α preconditioning. Differentiation of transplanted BMSCs, were significantly increased in preconditioning group. Although BMSCs without SDF-1 preconditioning exhibited remarkable recovery of pancreatic islets structure but this recovery were significantly increased in the BMSCs with SDF-1α preconditioning. Conclusion: Our results showed the effectiveness of SDF-1αpreconditioning in BMSCs transplantation of STZ induced diabetes mice which might be achieved through improvement of BMSCs homing into the injured pancreas. [ABSTRACT FROM AUTHOR]