Issue 4, 2005
From the journal:

Lab on a Chip

Human neural stem cell growth and differentiation in a gradient-generating microfluidic device†

Bong Geun Chung,‡a   Lisa A. Flanagan,‡b   Seog Woo Rhee,a   Philip H. Schwartz,cd   Abraham P. Lee,a   Edwin S. Monuki*bc  and  Noo Li Jeon*a  

* Corresponding authors

a Department of Biomedical Engineering, Henry Samueli School of Engineering, University of California Irvine, Irvine, CA 92697-2715, USA
E-mail: njeon@uci.edu
Fax: 1-949-824-9968
Tel: 1-949-824-9032

b Department of Pathology, College of Medicine, University of California Irvine, Irvine, CA 92697-4800, USA
E-mail: emonuki@uci.edu
Fax: 1-949-824-2160
Tel: 1-949-824-9604

c Department of Developmental and Cell Biology, School of Biological Sciences, University of California Irvine, Irvine, CA, USA

d National Human Neural Stem Cell Resource, Children's Hospital of Orange County Research Institute, Orange, CA, USA

Abstract

This paper describes a gradient-generating microfluidic platform for optimizing proliferation and differentiation of neural stem cells (NSCs) in culture. Microfluidic technology has great potential to improve stem cell (SC) cultures, whose promise in cell–based therapies is limited by the inability to precisely control their behavior in culture. Compared to traditional culture tools, microfluidic platforms should provide much greater control over cell microenvironment and rapid optimization of media composition using relatively small numbers of cells. Our platform exposes cells to a concentration gradient of growth factors under continuous flow, thus minimizing autocrine and paracrine signaling. Human NSCs (hNSCs) from the developing cerebral cortex were cultured for more than 1 week in the microfluidic device while constantly exposed to a continuous gradient of a growth factor (GF) mixture containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2) and platelet-derived growth factor (PDGF). Proliferation and differentiation of NSCs into astrocytes were monitored by time-lapse microscopy and immunocytochemistry. The NSCs remained healthy throughout the entire culture period, and importantly, proliferated and differentiated in a graded and proportional fashion that varied directly with GF concentration. These concentration-dependent cellular responses were quantitatively similar to those measured in control chambers built into the device and in parallel cultures using traditional 6-well plates. This gradient-generating microfluidic platform should be useful for a wide range of basic and applied studies on cultured cells, including SCs.

Graphical abstract: Human neural stem cell growth and differentiation in a gradient-generating microfluidic device

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Article information

DOI
https://doi.org/10.1039/B417651K
Article type
Paper
Submitted
22 Nov 2004
Accepted
17 Feb 2005
First published
09 Mar 2005

Lab Chip, 2005,5, 401-406

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Human neural stem cell growth and differentiation in a gradient-generating microfluidic device

B. G. Chung, L. A. Flanagan, S. W. Rhee, P. H. Schwartz, A. P. Lee, E. S. Monuki and N. L. Jeon, Lab Chip, 2005, 5, 401 DOI: 10.1039/B417651K

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