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内容記述 |
AbstractBackgroundEffective treatments for cerebral palsy caused by Hypoxic-ischemic encephalopathy are urgently needed. Current therapies primarily include prevention or acute intervention, leaving a major gap in the options for reversing established neurologic damage. Because of their ease of collection and unique trophic factor profile,stem cells from human exfoliated deciduous teeth (SHED) are promising candidates for cell-based therapy targeting neurological disorders. In this study, we examined the therapeutic potential of SHED in a rat model of cerebral palsy,focusing on neurogenic and functional recovery.MethodsHypoxic–ischemic encephalopathy was induced in neonatal rats using the Rice–Vannucci method.Rats with motor impairments received intravenous SHED injections, whereas the control group received a vehicle solution. Behavioral tests assessed motor coordination and cognitive performance. Proteomic analyses andimmunohistochemistry were performed to examine the underlying mechanisms. The migration and biodistribution of SHED were tracked using quantum dot-labeled SHED with in vivo imaging. Neural stem cells were cocultured withSHED to evaluate neurogenesis, followed by RNA sequencing and the analysis of trophic factors in the conditioned media.ResultsSHED treatment significantly ameliorated motor coordination, memory, and learning. Proteomic analysis revealed increased expression of proteins associated with neurogenesis in the SHED group. Histopathologicevaluations revealed enhanced neurogenesis in the hippocampal dentate gyrus and subventricular zone 2 weeks posttreatment, with increased NeuN-positive cells in the hippocampus and cortex at ten weeks. In vivo imaging revealed the migration of quantum dot-labeled SHED to the brain. Neural stem cells co-cultured with SHED in vitro exhibited higher proliferation rates. The SHED-conditioned medium contained increased levels of hepatocyte growthfactor (HGF), and HGF-neutralizing antibodies suppressed the enhanced cell proliferation. RNA sequencing revealed significant alterations in genes associated with the PI3K–Akt signaling pathway. |
