Functional immobilization of interferon-gamma induces neuronal differentiation of neural stem cells.
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.
Leipzig
Nic D
ND
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
Xu
Changchang
C
Zahir
Tasneem
T
Shoichet
Molly S
MS
D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002234:Carbodiimides / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology; D005898:Glass / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D007371:Interferon-gamma / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013388:Succinimides / Q000737:chemistry; D013499:Surface Properties
D000178:Acrylamides; D019208:Brain-Derived Neurotrophic Factor; D002234:Carbodiimides; D020100:Hydrogels; D013388:Succinimides; D004921:Erythropoietin; D007371:Interferon-gamma; C035761:N-hydroxysulfosuccinimide; D048271:Chitosan; C045985:methacrylamide