Abstract
ABSTRACTBackgroundTransplantation of human cranial bone-derived mesenchymal stem cells (hcMSCs) in patients with central nervous system disorders may improve motor function through high neurotrophic factor expression. However, the effects of hcMSCs cultured under microgravity (MG) conditions on cerebral infarction remain unclear. Thus, this study investigated the transplantation effects of hcMSCs cultured in a simulated MG environment on cerebral infarction model rats.MethodsFor immunohistological analysis and neurological function evaluation, hcMSCs cultured in normal gravity (1G) or MG environment were transplanted in rats 1 day after inducing cerebral infarction. The expression of endogenous neurotrophic; axonal, neuronal, and synaptogenic; angiogenic; and apoptosis-related factors in infarcted rat brain tissue was examined by real-time polymerase chain reaction (PCR) and western blotting analyses 35 days after stroke induction. MicroRNAs (miRNAs) of hcMSCs cultured under 1G or MG environments were sequenced.ResultsNeurological function was significantly improved after transplantation of hcMSCs from the MG group compared with that from the 1G group. Protein expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the MG group than in the 1G group, whereas sortilin 1 expression was significantly lower. MiRNA 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.ConclusionsThese results indicate that hcMSCs cultured in an MG environment may be a useful source of stem cells for the recovery of neurological function in cerebral infarction patients.
Publisher
Cold Spring Harbor Laboratory