Vascular defects associated with hereditary hemorrhagic telangiectasia revealed in patient-derived isogenic iPSCs in 3D vessels on chip
Valeria V. Orlova, Dennis M. Nahon, Amy Cochrane, Xu Cao, Christian Freund, Francijna van den Hil, Cornelius J.J. Westermann, Repke J. Snijder, Johannes Kristian Ploos van Amstel, Peter ten Dijke, Franck Lebrin, Hans‐Jurgen Mager, Christine L. Mummery
Abstract
-hiPSC-ECs and the healthy isogenic control behaved similarly in two-dimensional (2D) culture, forming functionally indistinguishable vascular networks. However, when grown in 3D organ-on-chip devices under microfluidic flow, lumenized vessels formed in which defective vascular organization was evident: interaction between inner ECs and surrounding pericytes was decreased, and there was evidence for vascular leakage. Organs on chip thus revealed features of HHT in hiPSC-derived blood vessels that were not evident in conventional 2D assays.