Treatment of rat brain ischemia model by NSCs-polymer scaffold transplantation

Abstract

Abstract Neural stem cells (NSCs) transplantation is a promising therapeutic strategy for ischemic stroke. However, significant cell death after transplantation greatly limits its effectiveness. Poly (trimethylene carbonate)15-F127-poly (trimethylene carbonate)15 (PTMC15-F127-PTMC15, PFP) is a biodegradable thermo-sensitive hydrogel biomaterial, which can control drug release and provide permissive substrates for donor NSCs. In our study, we seeded NSCs into PFP polymer scaffold loaded with three neurotrophic factors, including brain-derived neurotrophic factor, nerve growth factor, and Neurotrophin-3. And then we transplanted this NSCs-polymer scaffold in rat brains 14 days after middle cerebral artery occlusion. ELISA assay showed that PFP polymer scaffold sustained releasing three neurotrophic factors for at least 14 days. Western Blot and fluorescence immunostaining revealed that NSCs-polymer scaffold transplantation significantly reduced apoptosis of ischemic penumbra and promoted differentiation of the transplanted NSCs into mature neurons. Furthermore, infarct size was reduced, and neurological performance of the animals were improved by the transplanted NSCs-polymer scaffold. These results demonstrate that PFP polymer scaffold loaded with neurotrophic factors can enhance the effectiveness of stem cell transplantation therapy, which provides a new way for cell transplantation therapy in ischemic stroke.