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Review
. 2017 May 8;3(2):FSO187.
doi: 10.4155/fsoa-2016-0091. eCollection 2017 Jun.

Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip

Jie Zhang  1   1 , Xiaofeng Wei  1   1 , Rui Zeng  1   1 , Feng Xu  2   2 , XiuJun Li  1   3   4   1   3   4
Affiliations
Review

Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip

Jie Zhang et al. Future Sci OA. .

Abstract

Microfluidic lab-on-a-chip provides a new platform with unique advantages to mimic complex physiological microenvironments in vivo and has been increasingly exploited to stem cell research. In this review, we highlight recent advances of microfluidic devices for stem cell culture and differentiation toward the development of organ-on-a-chip, especially with an emphasis on vital innovations within the last 2 years. Various aspects for improving on-chip stem-cell culture and differentiation, particularly toward organ-on-a-chip, are discussed, along with microenvironment control, surface modification, extracellular scaffolds, high throughput and stimuli. The combination of microfluidic technologies and stem cells hold great potential toward versatile systems of 'organ-on-a-chip' as desired. Adapted with permission from [1-8].

Keywords: microfluidic devices; organ-on-a-chip; stem cell; stem cell culture; stem cell differentiation.

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Conflict of interest statement

Financial & competing interests disclosure The authors would like to acknowledge the financial support of the NIH/NIAID under award number R21AI107415 and the NIH/NIGMS under award number SC2GM105584. Financial support from the US NSF-PREM program (DMR 1205302), the IDR Program at the UTEP and the NIH RCMI Pilot Grant is also gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Stem cell culture in microfluidic platforms.
(A) Precise control of shear stress on a single stem cell in a microfluidic device, which established a clonality validated stem cell line after tracing its growth at the single cell level. Reproduced with permission from [1] © Elsevier (2014). (B) Polydopamine coating on PDMS for stabilized MSC adhesion and multipotency. Reproduced with permission from [2] © Nature Publishing Group (2015). (C) Imparting alignment in ECM components in 3D hydrogels to orient outgrowth of neuronal processes. Reproduced with permission from [3] © Nature Publishing Group (2015). (D) A high-throughput microfluidic array containing 8100 culture chambers for hPSC culture and screening of candidate biologicals. Reproduced with permission from [4] © Nature Publishing Group (2016). ECM: Extracellular matrix; HDMA: High-density microbioreactor array; hPSC: Human pluripotent stem cell; MSC: Mesenchymal stem cell; PDMS: Polydimethylsiloxane.
<b>Figure 1.</b>
Figure 1.. Stem cell culture in microfluidic platforms.
(A) Precise control of shear stress on a single stem cell in a microfluidic device, which established a clonality validated stem cell line after tracing its growth at the single cell level. Reproduced with permission from [1] © Elsevier (2014). (B) Polydopamine coating on PDMS for stabilized MSC adhesion and multipotency. Reproduced with permission from [2] © Nature Publishing Group (2015). (C) Imparting alignment in ECM components in 3D hydrogels to orient outgrowth of neuronal processes. Reproduced with permission from [3] © Nature Publishing Group (2015). (D) A high-throughput microfluidic array containing 8100 culture chambers for hPSC culture and screening of candidate biologicals. Reproduced with permission from [4] © Nature Publishing Group (2016). ECM: Extracellular matrix; HDMA: High-density microbioreactor array; hPSC: Human pluripotent stem cell; MSC: Mesenchymal stem cell; PDMS: Polydimethylsiloxane.
<b>Figure 2.</b>
Figure 2.. Stem cell differentiation on microfluidic devices.
(A) Core–shell hydrogel droplets for culture and differentiation of hNSCs. Matrigel was coated on the inside surface to mimic the basal membrane. Reproduced with permission from [5] © The Royal Society of Chemistry (2016). (B) Combined mechanical, electrical and biochemical stimulations for hMSC differentiation. Reproduced with permission from [6] © the Nature Publishing Group (2015). hMSC: Human mesenchymal stem cell; hNSC: Human neural stem cell.
<b>Figure 3.</b>
Figure 3.. Stem cell-based organ-on-a-chip construction.
(A) Differentiation of hiPSC-derived human neuroepithelial cells into functional dopaminergic neurons in microchannels. Reproduced with permission from [7] © The Royal Society of Chemistry (2015). (B) Generation of 3D functional microvascular networks with hMSCs in a microfluidic system. Reproduced with permission from [8] © The Royal Society of Chemistry (2014). hiPSC: Human-induced pluripotent stem cell; hMSC: Human mesenchymal stem cell.
See this image and copyright information in PMC

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