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

Stem Cell Reports, vol. 16, pp. 2159–2168

Abstract

Crosstalk 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 Ca 2+ 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.

Authors 7

1. Marc Vila Cuenca Aachen Department of Anatomy and Embryology Department of Clinical Genetics

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands; Department of Clinical Genetics, Leiden University Medical Center, 2333ZA Leiden, the Netherlands

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands

   Department of Clinical Genetics, Leiden University Medical Center, 2333ZA Leiden, the Netherlands

2. Amy Cochrane Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands

3. Francijna E. van den Hil Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands

4. Antoine A.F. de Vries Aachen Department of Cardiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Cardiology, Leiden University Medical Center, 2333ZA Leiden, the Netherlands

5. Saskia A.J. Lesnik Oberstein Aachen Department of Clinical Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Genetics, Leiden University Medical Center, 2333ZA Leiden, the Netherlands

6. Christine L. Mummery Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands

7. Valeria V. Orlova corresponding Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands. Electronic address: v.orlova@lumc.nl

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZA Leiden, the Netherlands