Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis

Table 1 Features of microfluidic techniques for stem cell engineering

Features of microfluidic technology	Solutions	Stem cell applications	Ref.
Cell or ECM patterning	Microchannel	Co-culture of hMSCs and hNSCs	Yang et al[34], 2015
	Microwell-patterned substrate	Co-culture of hESCs and fibroblasts	Khademhosseini et al[35], 2006
Chemical gradient	Multichannel array	Regulation of hematopoietic stem cell fates	Mahadik et al[26], 2014
	Overlapping gradients	Neuronal commitment of mouse ESCs	Cosson et al[37], 2013
	Sink and source channel with continuous flow	Chemotaxis of NSCs	Xu et al[38], 2013
Cell-cell or cell-ECM interaction	Microchannel-groove	Monitoring of differentiation and migration of NSCs derived from hESCs	Lee et al[39], 2013
Shear stress	Flow	Behavior observation of MSCs	Zheng et al[40], 2012
Droplet	Encapsulation and emulsion	Construction of ADSC microenvironment	Sakai et al[41], 2011
		Construction of pre-hatching embryo	Agarwal et al[42], 2013
Sorting and separation	Optical tweezer	Sorting of hESCs	Wang et al[43], 2013
	Electrical impedance flow	Identifying the differentiation of state of single cell	Song et al[44], 2013
	Multiple dielectrophoresis	Sorting of hMSCs	Song et al[45], 2015
Hydrodynamic trapping	Chamber array	EB-trap array	Suri, et al[46], 2013
Integration and automation	Multi-arrayed chips and integrated systems (e.g., liquid handler, cell chamber, imaging system, software)	Automatic culture of stem cell-derived dopaminergic neurons	Kane et al[47], 2019
		Investigation of dynamic changes of hematopoietic stem cell condition	Dettinger et al[48], 2018
		Clonal analysis of hESCs differentiation pattern	Sikorski et al[49], 2015
Mechanical and electrical actuators	Mechanical stretch	Stretch-activated stem cell differentiation	He et al[51], 2018
	Magnetic resonance	Quantification of metabolic flux in leukemia stem cells	Jeong et al[52], 2017

ECMs: Extracellular matrixes; hMSC: Human mesenchymal stem cell; hESC: Human embryonic stem cell; NSC: Neural stem cell; ADSC: Adipose-derived stem cell; EB: Embryoid body.