Synergistic effects of neural stem cells and ibrutinib on neural tissue repair and functional recovery in a contusion mouse model of spinal cord injury

Modulating the immune response following spinal cord injury (SCI) is vital for establishing a conducive microenvironment that supports the survival and engraftment of transplanted neural stem/progenitor cells (NSPCs). Building on our prior findings of ibrutinib's immunotherapeutic potential in acute SCI, this study investigates the impact of ibrutinib administration on NSPC survival, fate and their potential synergistic effects on tissue repair and motor function in a contusive mouse model of SCI. Green fluorescence expressing NSPCs were transplanted into the lesion site with or without concurrent ibrutinib administration. Over four weeks, comprehensive assessments included behavioral evaluations, lesion volume measurements, and analyses of the survival, fate, and migration patterns of the transplanted cells. The results revealed that ibrutinib and NSPCs individually reduced lesion volume and improved motor functions. However, their combination significantly accelerated and enhanced motor recovery. Furthermore, ibrutinib improved cell viability, increasing markers for oligodendrocyte and neuroblast while concurrently diminishing the expression of astrocyte marker glial fibrillary acidic protein (GFAP). In conclusion, the combined utilization of ibrutinib and NSPC transplantation presents a promising strategy for enhancing tissue repair, promoting functional recovery, and positively modulating cell behaviors in the context of SCI.