Copyright ©The Author(s) 2019.
World J Stem Cells. Oct 26, 2019; 11(10): 803-816
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.803
Table 1 Features of microfluidic techniques for stem cell engineering
Features of microfluidic technologySolutionsStem cell applicationsRef.
Cell or ECM patterningMicrochannelCo-culture of hMSCs and hNSCsYang et al[34], 2015
Microwell-patterned substrateCo-culture of hESCs and fibroblastsKhademhosseini et al[35], 2006
Chemical gradientMultichannel arrayRegulation of hematopoietic stem cell fatesMahadik et al[26], 2014
Overlapping gradientsNeuronal commitment of mouse ESCsCosson et al[37], 2013
Sink and source channel with continuous flowChemotaxis of NSCsXu et al[38], 2013
Cell-cell or cell-ECM interactionMicrochannel-grooveMonitoring of differentiation and migration of NSCs derived from hESCsLee et al[39], 2013
Shear stressFlowBehavior observation of MSCsZheng et al[40], 2012
DropletEncapsulation and emulsionConstruction of ADSC microenvironmentSakai et al[41], 2011
Construction of pre-hatching embryoAgarwal et al[42], 2013
Sorting and separationOptical tweezerSorting of hESCsWang et al[43], 2013
Electrical impedance flowIdentifying the differentiation of state of single cellSong et al[44], 2013
Multiple dielectrophoresisSorting of hMSCsSong et al[45], 2015
Hydrodynamic trappingChamber arrayEB-trap arraySuri, et al[46], 2013
Integration and automationMulti-arrayed chips and integrated systems (e.g., liquid handler, cell chamber, imaging system, software)Automatic culture of stem cell-derived dopaminergic neuronsKane et al[47], 2019
Investigation of dynamic changes of hematopoietic stem cell conditionDettinger et al[48], 2018
Clonal analysis of hESCs differentiation patternSikorski et al[49], 2015
Mechanical and electrical actuatorsMechanical stretchStretch-activated stem cell differentiationHe et al[51], 2018
Magnetic resonanceQuantification of metabolic flux in leukemia stem cellsJeong et al[52], 2017
Table 2 High-throughput screening analysis for stem cell engineering
Techniques for high-throughput screeningAdvantagesApplicationsCell typesRef.
Microarray techniqueCell encapsulation in hydrogel-matrix spots; minimal consumption of cells and reagentsToxicity and phenotypic screening of NPCsNPCsNierode et al[60], 2016
Studying of the expansion of mouse ESCESCsFernandes et al[62], 2009
Microencapsulation using microfluidic flow focusingMultiple generation of 3D cellsStudy of embryogenesisiPSCsAgarwal et al[42], 2013
Encapsulation of cells and ECMs; controlled physicochemical properties of gel beadsStudy of ESC expansionmESCsAllazetta et al[63], 2013
Co-culture of pancreatic islets and hMSCshMSCsHeaden et al[64], 2014
Silicon stamp for spotting proteinControl of gel stiffness for stem cell fatesStudy of stem cell nichehMSCsGobaa et al[65], 2011
ECM arrayMimicking of microenvironmentsStudy of stem cell nichehASCsBeachley et al[66], 2015
Microwell array using thermoformed cyclic olefin polymerRound-bottom array, uniform size of well arrayEB generationmESCsVrij et al[67], 2016
Micro droplet array; hydrophobic-hydrophilic surfaceRobotics-free sample handling; high throughput; low reagent consumption; high-content readoutsScreening of iPSC pluripotency and proliferationiPSCsZhang et al[68], 2016
Serial dilution generatorGeneration of different concentration, combination and temporal sequence of drugsEffect of cytokine (Tgfβ3) on hBM-MSChBM-MSCOcchetta et al[69], 2015
Microraft arrayMimicking of microenvironments and enhancement of contactStudy of stem cell fate by mimicking nicheIntestinal stem cellsGracz et al[70], 2015
Micropattern-well hybridCompatibility of HCSScreening of stem cell differentiation and drug screeningNPCsYu et al[71], 2018
Table 3 High-throughput screening-based three-dimensional organ- or organoid-on-a-chip
Organ typePlatform typeCell typeApplicationsRef.
LiverOrgan-on-a-chipHuman iPSC -hepatocytesScreening of hepatotoxic drugsWare et al[74], 2015
Organ-on-a-chipHepatocyte-ESC lineCo-culture of multi-organMaterne et al[75], 2015
Organoid-on-a-chipiPSCsTests of liver functionSchepers et al[76], 2016
HeartOrgan-on-a-chipHuman iPSC -cardiomyocytesScreening of molecular inducer related to cardiac myocyte proliferationTitmarsh et al[83], 2016
Human iPSC - cardiomyocytesModeling of mitochondrial cardiomyopathy of Barth syndromeWang et al[84], 2014
Organoid-on-a-chiphPSCsStudy of cardiac maturationMills et al[86], 2017
BrainOrgan-on-a-hipNPCsToxicity test with in vitro brain model of Alzheimer’s diseasePark et al[91], 2015
NPCsCalcium assayLai et al[92], 2012
NPCsIn vitro test for Alzheimer’s diseaseYu et al[71], 2018
Organoid-on-a-chipHuman iPSCModel of neurodevelopment disorder by prenatal nicotine exposureWang et al[93], 2018
Organ-on-a-chipHuman iPSCHigh-throughput compound evaluation on three-dimensional networks of neurons and gliaWevers et al[94], 2016
IntestineOrganoid-on-a-chipHuman iPSCStudy of response to exogenous stimuliWorkman et al[97], 2018
KidneyOrganoid-on-a-chipHuman iPSCHigh-throughput screening format organoids for multidimensional phenotypic screeningCzerniecki et al[100], 2018