Human cranial bone-derived mesenchymal stem cells cultured under microgravity can improve cerebral infarction in rats

Transplantation of human cranial bone-derived mesenchymal stem cells (hcMSCs) in central nervous system disorders has the potential to improve motor function by highly expressing neurotrophic factors. However, the effects of hcMSCs cultured under microgravity (MG) conditions on cerebral infarction have not been investigated before. Thus, this study aimed to investigate the transplantation effects of hcMSCs cultured in a simulated MG environment on cerebral infarction model rats. Our results showed that neurological function was significantly improved after transplantation of hcMSCs cultured in the MG environment (MG group) compared with normal gravity environment (1G group). Protein expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the MG group than in the IG group, whereas sortilin 1 expression was significantly lower. MicroRNA analysis revealed that genes related to cell proliferation, angiogenesis, neurotrophy, anti-apoptosis, neural and synaptic organization, and cell differentiation inhibition were significantly upregulated in the MG group. In contrast, genes promoting microtubule and extracellular matrix formation and cell adhesion, signaling, and differentiation were downregulated. These results indicate that hcMSCs cultured in an MG environment may be a useful source of stem cells for recovery of neurological function after cerebral infarction. Overall design: Cerebral infarction model rats were generated; hcMSCs cultured in normal gravity (1G) or MG environment were transplanted via the transvenous route on the first day after induction of cerebral infarction for immunohistological analysis and neurological function evaluation. The expression of endogenous neurotrophic factors, axonal, neuronal, and synaptogenic factors, angiogenic factors, and apoptosis-related factors in infarcted brain tissue at 35 days after stroke induction was examined by real-time polymerase chain reaction (PCR) and western blotting analyses. Sequencing analysis of miRNAs was performed in hcMSCs cultured under 1G or MG environments.