Functional immobilization of interferon-gamma induces neuronal differentiation of neural stem cells

Abstract

Stem cell transplantation provides significant promise to regenerative strategies after injury in the central nervous system. Neural stem/progenitor cells (NSPCs) have been studied in terms of their regenerative capacity and their ability to differentiate into neurons when exposed to various soluble factors. In this study, interferon-gamma (IFN-gamma) was compared with brain-derived neurotrophic factor (BDNF) and erythropoietin and was shown to be the best single growth factor for inducing neuronal differentiation from adult rat brain-derived NSPCs. Next, IFN-gamma was surface immobilized to a methacrylamide chitosan (MAC) scaffold that was specifically designed to match the modulus of brain tissue and neuronal differentiation of NSPCs was examined in vitro by immunohistochemistry. Bioactive IFN-gamma was successfully immobilized and quantified by ELISA. Both soluble and immobilized IFN-gamma on MAC surfaces showed dose dependent neuronal differentiation with soluble saturation occurring at 100 ng/mL and the most effective immobilized IFN-gamma dose at 37.5 ng/cm(2), where significantly more neurons resulted compared with controls including soluble IFN-gamma.