期刊
BIOMATERIALS
卷 30, 期 36, 页码 6867-6878出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.09.002
关键词
Neural stem cells; Substrate stiffness; Hydrogel scaffolds; Chitosan; Neurons; Oligodendrocytes
资金
- Natural Sciences and Engineering Research Council of Canada
- Ontario Ministry of Research and Innovation postdoctoral fellowship (NDL)
- Advanced Food and Materials Network
Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal and differentiation. In order to better understand the contribution of substrate stiffness to neural stem/progenitor cell (NSPC) differentiation and proliferation, a photopolymerizable methacrylamide chitosan (MAC)biomaterial was developed. Photopolymerizable MAC is particularly compelling for the study of the central nervous system stem cell niche because Young's elastic modulus (E-Y) can be tuned from less than 1 kPa to greater than 30 kPa. Additionally, the numerous free amine functional groups enable inclusion of biochemical signaling molecules that, together with the mechanical environment, influence cell behavior. Herein, NSPCs proliferated on MAC substrates with Young's elastic moduli below 10 kPa and exhibited maximal proliferation on 3.5 kPa surfaces. Neuronal differentiation was favored on the softest surfaces with E-Y < 1 kPa as confirmed by both immunohistochemistry and qRT-PCR. Oligodendrocyte differentiation was favored on stiffer scaffolds (>7 kPa); however, myelin oligodendrocyte glycoprotein (MOG) gene expression suggested that oligodendrocyte maturation and myelination was best on <1 kPa scaffolds where more mature neurons were present. Astrocyte differentiation was only observed on < 1 and 3.5 kPa surfaces and represented less than 2% of the total cell population. This work demonstrates the importance of substrate stiffness to the proliferation and differentiation of adult NSPCs and highlights the importance of mechanical properties to the success of scaffolds designed to engineer central nervous system tissue. (C) 2009 Elsevier Ltd. All rights reserved.
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