Human induced pluripotent stem cell-derived vessels as dynamic atherosclerosis model on a chip

Abstract

Atherosclerosis is an arterial disease characterized by intravascular plaques. Disease hallmarks are vessel stenosis and hyperplasia, eventually escalating into plaque rupture and acute clinical presentations. Innate immune cells and local variations in hemodynamics are core players in the pathology, but their mutual relationship has never been investigated before due to the lack of modeling systems with adequate degree of complexity. Here, we combined computational fluid dynamics and tissue-engineering to achieve, for the first time in vitro, full atherosclerotic plaque development. Our model incorporates induced pluripotent stem cell-derived populations into small-caliber arteries that are cultured in atheroprone conditions. Using machine-learning-aided immunophenotyping, molecular and nanoprobe-based tensile analyses, we found that immune cells, extracellular matrix components and tensional state were comparable between in vitro and ex vivo human lesions. Our results provide further insights into the relation between hemodynamics and inflammation, introducing a versatile, scalable modeling tool to study atherosclerosis onset and progression.