Injection of Stromal Cell-Derived Factor-1 (SDF-1) Nanoparticles After Traumatic Brain Injury Stimulates Recruitment of Neural Stem Cells

Abstract

Traumatic brain injury (TBI) usually results from direct mechanical damage to the brain, which leads to degeneration and death of the central nervous system (CNS). The migration of neural stem/progenitor cells (NSCs) to brain is essential to various physiological and pathological processes of the CNS. Therefore, NSCs are considered as a promising alternative option for neurological diseases. SDF-1α is one of known chemokines whose receptor CXCR4 is detected in the CNS. We explored the efficacy of nanoparticles loaded with SDF-1 on TBI and analyzed its potential mechanism. After synthesis of SDF-1-loaded microspheres (MS) and -nanoparticles and establishment of animal model of TBI, 50 modeled mice were randomly injected with MS bovine serum albumin (BSA), MS SDF1, or SDF1-loaded nanoparticles and 10 TBI animals were taken as control group. After that, we observed the lesions and examined the characteristics of the nanoparticles and MS. Transwell assay and immunofluorescence were conducted to determine the migration and invasion upon treatments. Nanoparticles and MS encapsulated most of SDF-1, but MS released 100% SDF-1 and the nanoparticles alone released minority (25%) within 2 weeks. As only SDF-1 nanoparticles could induce NSCs to migrate to the injured area, this approach could enhance healing of the lesion with more NSCs around the lesion. Collectively, this study used particles to deliver SDF-1 to the central nervous system with nanoparticles having a longer-lasting release. Injection of nanoparticleloaded SDF-1 would retain the biological activity of SDF-1 and improve neuroblast migration, thereby improving the TBI condition. These findings show great prospect for nanoparticles application in brain injury.