Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells.

Marc Vila Cuenca,Antoine A.F De Vries,Christine L Mummery,Saskia A.J Lesnik Oberstein,Amy Cochrane,Valeria V Orlova,Francijna E Van Den Hil

doi:10.1016/j.stemcr.2021.08.003

Marc Vila Cuenca, Antoine A.F De Vries + Show 5 more

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https://doi.org/10.1016/j.stemcr.2021.08.003

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Journal: Stem cell reports	Publication Date: Sep 1, 2021
Citations: 54	License type: cc-by

Affiliation: Leiden University Medical Center

Abstract

SummaryCrosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-derived vascular cells self-organized to form stable microvascular networks reproducibly, in which the vessels were lumenized and functional, responding as expected to vasoactive stimulation. Vascular organization and intracellular Ca2+ release kinetics in VSMCs could be quantified using automated image analysis based on open-source software CellProfiler and ImageJ on widefield or confocal images, setting the stage for use of the platform to study vascular (patho)physiology and therapy.

Highlights

Crosstalk between endothelial cells (ECs) and mural cells is pivotal for proper function of many blood vessels
Human primary ECs, or Human induced pluripotent stem cells (hiPSCs)-ECs have been combined with human primary mural cells (Campisi et al, 2018; van Dijk et al, 2020; van Duinen et al, 2019) but not with mural cells derived from hiPSC, precluding opportunities to replicate vascular diseases originating in the mural cells
Characterization of the VoC model Using the commercially available AIM Biotech 3D cell culture chips, hiPSC-ECs (Halaidych et al, 2018; Orlova et al, 2014a, 2014b) were combined with hiPSC-vascular smooth muscle cells (VSMCs) (Halaidych et al, 2019), human brain vascular smooth muscle cells (HBVSMCs) or human brain vascular pericytes (HBVPs) (Figure 1Ai) in a fibrin hydrogel (Figure 1Aii) and the cell/gel mix was injected into the middle channel of the microfluidic chip (Figure 1Aiii)

Summary

Introduction

Crosstalk between endothelial cells (ECs) and mural cells (pericytes and vascular smooth muscle cells [VSMCs]) is pivotal for proper function of many blood vessels. Human induced pluripotent stem cells (hiPSCs) generated from heathy individuals and patients are a useful source of vascular cells and they do reflect the genetic background of the individual from whom they are derived (Samuel et al, 2015). Microfluidic devices have been engineered that do incorporate these features and provide the environment for the formation of multi-cell type 3D tissues and vessels-on-chip (VoC) (Tronolone and Jain, 2021). Primary human cells provide the closest mimic to human blood vessels but are of limited availability and of variable genetic origin (Tronolone and Jain, 2021). Human primary ECs, or hiPSC-ECs have been combined with human primary mural cells (Campisi et al, 2018; van Dijk et al, 2020; van Duinen et al, 2019) but not with mural cells derived from hiPSC, precluding opportunities to replicate (patient-specific) vascular diseases originating in the mural cells

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Discussion

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