Impact of Sleep Deprivation on Bone Marrow Mesenchymal Stem Cell-Mediated Remyelination in the Corpus Callosum of Male Mice Publisher



S Amirizadeh SHIVA ; I Ragerdi Kashani IRAJ ; R Asadigolshan REZA ; M Hashemi MAEDEH ; D Zarini DAVOOD ; P Javanbakht PARINAZ ; A Alikarami AMENEH ; M Shabani MARYAM ; P Pasbakhsh PARICHEHR
Source: Bratislava Medical Journal Published:2025

Abstract

Background: Multiple sclerosis (MS) is a neurological disorder that can cause a wide range of symptoms. Bone marrow mesenchymal stem cells (BMSCs) have shown promise in modulating immune responses and promoting tissue repair. However, the therapeutic efficacy of BMSCs is influenced by external factors, and the impact of sleep deprivation on their therapeutic efficacy remains unclear. This study investigated the influence of sleep deprivation on the regenerative potential of BMSCs in a mouse demyelination model induced by cuprizone. Methods and results: BMSCs were characterized using flow cytometry, confirming high expression of CD90 (99.9%) and CD44 (99.2%). We evaluated the effects of sleep deprivation (for 72 h) on the regenerative potential of intranasal injection of BMSCs (1 × 106 cells/kg in 12 µl). BMSC migration was tracked using fluorescence microscopy, and immunohistochemistry and RT-PCR were used to assess glial activation, microglial functional states, oligodendrocyte numbers, and neuroinflammatory markers. Motor function was evaluated to determine the therapeutic outcomes. BMSCs successfully migrated to the corpus callosum within 24 h. In subjected mice, BMSC therapy promoted a shift from a pro-inflammatory to a repair-associated state, enhanced oligodendrocyte regeneration, and improved motor performance. However, BMSCs derived from sleep-deprived donors exhibit diminished efficacy; they fail to resolve neuroinflammation, show reduced expression of repair-supportive markers (e.g., TREM2), decrease in oligodendrocyte numbers, and result in impaired functional recovery. Conclusion: Sleep deprivation significantly compromises the therapeutic efficacy of BMSCs in demyelination repair, underscoring the importance of sleep in supporting stem cell-mediated regeneration. These findings highlight the need to address sleep disturbances in stem cell donors and provide insights into optimizing regenerative strategies for the treatment of neurodegenerative disorders. © 2025 Elsevier B.V., All rights reserved.