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

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.

Intranasal Delivery of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Alleviates Memory Deficits In Sporadic Alzheimer’s Rat Models By Regulating Neurotrophic and Apoptotic Genes

“…This nding was assessed by measuring the levels of trophic factors and apoptosis-related factors in the hippocampus. In agreement with previous studies [24,33], the IN route of MSC delivery to the brain was more effective in the present study. In this regard, Danielyan et al examined the possible routes of IN-administered cells and hypothesized that these cells could bypass the BBB by migrating from the nasal mucosa through the cribriform plate along the olfactory neural pathway into the brain and CSF [21].…”

Intranasal Delivery of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Alleviate Memory Deficits In Sporadic Alzheimer’s Rat Model By Regulating Neurotrophic and Apoptosis Genes

“…In agreement with other studies [24,33], the IN route of MSC delivery to the brain in this study proved more effective. The possible migration routes of IN administered cells were studied by Danielyan and et.…”

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

“…Tgfb1 has been shown to promote remyelination in the adult CNS in addition to its classical proinflammatory role (Hamaguchi et al, 2019;Mota et al, 2020). Cxcr4 is a known regulator of remyelination in other models of infection and CNS inflammation (Carbajal et al, 2011;Tian et al, 2018;Beigi Boroujeni et al, 2020). The steady increase in myelination genes throughout the kinetics of chronic T. gondii infection demonstrates a possible role of myelination in maintaining neuronal signaling and function to prohibit worsening of neuropathology as well as the possibility of remyelination to heal pathology or reorganize neuronal circuits (David et al, 2016).…”