Neural stem cell (NSC) transplantation has great therapeutic potential for neurodegenerative diseases and central nervous system injuries. Successful NSC replacement therapy requires precise control over the cellular behaviors. However, the regulation of NSC fate is largely unclear, which severely restricts the potential clinical applications. To develop an effective model, we designed an assembled microfluidic system to engineer NSC niches and assessed the effects of various culture conditions on NSC fate determination. Five types of NSC microenvironments, including two-dimensional (2D) cellular monolayer culture, 2D cellular monolayer culture on the extracellular matrix (ECM), dispersed cells in the ECM, three-dimensional (3D) spheroid aggregates, and 3D spheroids cultured in the ECM, were constructed within an integrated microfluidic chip simultaneously. In addition, we evaluated the influence of static and perfusion culture on NSCs. The efficiency of this approach was evaluated comprehensively by characterization of NSC viability, self-renewal, proliferation, and differentiation into neurons, astrocytes, or oligodendrocytes. Differences in the status and fate of NSCs governed by the culture modes and micro-niches were analyzed. NSCs in the microfluidic device demonstrated good viability, the 3D culture in the ECM facilitated NSC self-renewal and proliferation, and 2D culture in the static state and spheroid culture under perfusion conditions benefited NSC differentiation. Regulation of NSC self-renewal and differentiation on this microfluidic device could provide NSC-based medicinal products and references for distinct nerve disease therapy.
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January 2017
Research Article|
January 25 2017
Microfluidic engineering of neural stem cell niches for fate determination
Yachen Wang
;
Yachen Wang
a)
1Department of Neurology,
The First Affiliated Hospital of China Medical University
, Shenyang, China
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Jingyun Ma;
Jingyun Ma
a)
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Na Li;
Na Li
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Liang Wang;
Liang Wang
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Liming Shen;
Liming Shen
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Yu Sun;
Yu Sun
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Yajun Wang;
Yajun Wang
3College of Life Science,
Liaoning Normal University
, Dalian, China
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Jingyuan Zhao;
Jingyuan Zhao
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Wenjuan Wei;
Wenjuan Wei
2Regenerative Medicine Center,
The First Affiliated Hospital of Dalian Medical University
, Dalian, China
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Yan Ren;
Yan Ren
b)
1Department of Neurology,
The First Affiliated Hospital of China Medical University
, Shenyang, China
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a)
Y. Wang and J. Ma contributed equally to this work.
b)
Authors to whom correspondence should be addressed. Y. Ren, No. 155 Nanjing Road, Shenyang, China, and J. Liu, No. 222 Zhongshan Road, Dalian, China. Electronic addresses: [email protected] and [email protected].
Biomicrofluidics 11, 014106 (2017)
Article history
Received:
November 27 2016
Accepted:
January 04 2017
Citation
Yachen Wang, Jingyun Ma, Na Li, Liang Wang, Liming Shen, Yu Sun, Yajun Wang, Jingyuan Zhao, Wenjuan Wei, Yan Ren, Jing Liu; Microfluidic engineering of neural stem cell niches for fate determination. Biomicrofluidics 1 January 2017; 11 (1): 014106. https://doi.org/10.1063/1.4974902
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