Apelin-overexpressing neural stem cells in conjunction with a silk fibroin nanofiber scaffold for the treatment of traumatic brain injury

Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries of the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a tussah silk fibroin nanofiber scaffold (TSFNS) that simulated the extracellular matrix (ECM) in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control, NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence and western blot (WB) experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and promoted the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier (BBB) damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.