Sodium alginate/collagen/stromal cell-derived factor-1 neural scaffold loaded with BMSCs promotes neurological function recovery after traumatic brain injury

Abstract

Stem cell therapy is promising for neural repair in devastating traumatic brain injury (TBI). However, the low survival and differentiation rates of transplanted stem cells are main obstacles to efficient stem cell therapy in TBI. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are key factors that regulate the survival, recruitment, and differentiation of stem cells. Herein, we synthesized a sodium alginate (SA)/collagen type I (Col)/SDF-1 hydrogel and investigated whether the SA/Col/SDF-1 hydrogel loaded with bone marrow-derived mesenchymal stem cells (BMSCs) had therapeutic effects on a TBI model. Our results showed that the SA/Col/SDF-1 scaffold could stably release SDF-1 and provide biocompatible and biodegradable microenvironment for the survival, migration, and neuronal differentiation of BMSCs in vitro. In a rat model of TBI, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated motor and cognition dysfunction and relieved anxiety and depressive-like behaviors. In addition, the BMSCs/SA/Col/SDF-1 scaffold reduced brain lesions and neuronal cell death and mitigated neuroinflammation. Further studies demonstrated that the BMSCs/SA/Col/SDF-1 hydrogel promoted the migration of BMSCs in the lesions and partly enhanced neurogenesis by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Taken together, our results indicate that the SA/Col/SDF-1 scaffold loaded with BMSCs exerts neuroreparative effects in a TBI rat model, and thus, it may serve as an alternative neural regeneration scaffold for brain injury repair. STATEMENT OF SIGNIFICANCE: Hydrogel facilitates the biological behaviors of transplanted stem cells for tissue regeneration. In this study, we synthesized sodium alginate (SA)/collagen type I (Col)/ scaffold to simultaneously deliver stromal cell derived factor-1 (SDF-1) and bone marrow mesenchymal stem cells (BMSCs) in a rat model of traumatic brain injury (TBI). We found that the SA/Col/SDF-1 hydrogel could continuously release SDF-1 and was conducive to the survival, migration and neuronal differentiation of BMSCs in vitro. In addition, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated neurological deficits, mitigated neuroinflammation, promoted the recruitment of BMSCs and enhanced neurogenesis in TBI partly by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Our results may serve as an alternative neural regeneration strategy for brain injury.

Keywords: Bone marrow-derived mesenchymal stem cells; Neurogenesis; Sodium alginate/collagen/stromal cell-derived factor-1 hydrogel; Sustained release; Traumatic brain injury.