The Effects of Microgravity on Differentiation and Regeneration in Neural Stem Cells

Neural stem cells (NSCs) are self-renewing, multipotent cells of the central nervous system (CNS) that can differentiate into a range of specialized cell types, including neurons, astrocytes, and oligodendrocytes (OLs). Due to their remarkable ability to self-renew and differentiate, NSCs hold immense potential for the treatment of neurodegenerative diseases (NDDs). However, clinical translation remains hindered by challenges such as expansion difficulties and phenotypic drift. This review synthesizes evidence on the divergent effects of microgravity on NSC biology. While real spaceflight has been shown to enhance NSC proliferation, it paradoxically reduces neurosphere volume. Microgravity simulations yield contrasting results: rotating wall vessel (RWV) systems promote neuron and astrocyte generation, whereas rotating cell culture systems (RCCSs) inhibit differentiation despite the use of pro-differentiation media. These phenotypic variations critically depend on experimental conditions, cell sources, and observation time. Future research should focus on elucidating cross-pathway interactions and optimizing culture parameters to enable clinical-scale NSC applications.