Biomol Ther  
Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient
Ji Hyeon Kim, Jiyeon Sim and Hyun-Jung Kim*
Laboratory of Molecular Pharmacology and Stem Cells, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
E-mail: hyunjungkim@cau.ac.kr
Tel: +82-2-820-5619, Fax: +82-2-820-5619
Received: January 2, 2018; Revised: January 22, 2018; Accepted: January 23, 2018; Published online: April 11, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro, we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.
Keywords: Neural stem cells, Microfluidic chip, Growth factor-gradient, Differentiation, Proliferation, Neurogenesis


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