SA/Col/SDF-1 Neural Scaffold Promotes the Homing of BMSCs and Functional Recovery in a Rat Model of Traumatic Brain Injury

Abstract

The low survival and differentiation rates of transplanted stem cells are the main obstacles to stem cell therapy in traumatic brain injury (TBI). Stromal cell derived factor-1 (SDF-1)/CXCR4 are key factors that regulate the cell activity, homing and differentiation of stem cells. Herein, we synthesized sodium alginate (SA)/collagen type I (Col)/SDF-1 hydrogel and investigated whether SA/Col/SDF-1 could improve the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) in TBI model. Our results showed that SA/Col/SDF-1 scaffold could continuously and stably release SDF-1 and provide a biocompatible and biodegradable microenvironment for the survival, migration and neuronal differentiation of BMSCs in vitro. In a rat model of TBI, SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated neurological deficits and relieved anxiety and depressive-like behaviors. In addition, BMSCs/SA/Col/SDF-1 scaffold could reduce brain lesion and neuronal cell death, as well as mitigate neuroinflammation. Further studies demonstrated that BMSCs/SA/Col/SDF-1 promoted the migration of BMSCs in the lesions and enhanced neurogenesis partly by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Taken together, our results indicate that SA/Col/SDF-1 scaffold enhances the neuroprotective effects of BMSCs in TBI rat model, which may serve as an alternative neural regeneration strategy for brain injury repair.