Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich, Leipzig, Germany; Medical Faculty, University of Leipzig, Leipzig, Germany
Michel Moussus
Helmholtz Pioneer Campus, Helmholtz Zentrum München, Munich, Germany
Matthias Meier
Helmholtz Pioneer Campus, Helmholtz Zentrum München, Munich, Germany; Centre for Biotechnology and Biomedicine, University of Leipzig, Leipzig, Germany; Corresponding author
Summary: The metabolic syndrome is accompanied by vascular complications. Human in vitro disease models are hence required to better understand vascular dysfunctions and guide clinical therapies. Here, we engineered an open microfluidic vessel-on-chip platform that integrates human pluripotent stem cell-derived endothelial cells (SC-ECs). The open microfluidic design enables seamless integration with state-of-the-art analytical technologies, including single-cell RNA sequencing, proteomics by mass spectrometry, and high-resolution imaging. Beyond previous systems, we report SC-EC maturation by means of barrier formation, arterial toning, and high nitric oxide synthesis levels under gravity-driven flow. Functionally, we corroborate the hallmarks of early-onset atherosclerosis with low sample volumes and cell numbers under flow conditions by determining proteome and secretome changes in SC-ECs stimulated with oxidized low-density lipoprotein and free fatty acids. More broadly, our organ-on-chip platform enables the modeling of patient-specific human endothelial tissue and has the potential to become a general tool for animal-free vascular research.
