The branching of life: human iPSC-based angiogenesis-on-chip

Abstract

This thesis establishes a human induced pluripotent stem cell-derived endothelial cell (hiPSC-EC)-based angiogenesis-on-chip (AoC) model to mimic vascular sprouting and test anti-angiogenic therapies. The system was optimized in a 3D microfluidic device that enabled the reproduction of sprout induction and functional validation with selective VEGFR2 inhibitors. The AoC assay demonstrated selective drug responses, with tyrosine kinase inhibitors effectively suppressing angiogenesis. Furthermore, patient-derived and gene-corrected hiPSCs from Hereditary Hemorrhagic Telangiectasia type 2 were generated with the purpose of investigating disease-relevant mechanisms leading to vascular malformations. Overall, this work advances promising, patient-specific in vitro vascular systems for mechanistic studies and preclinical therapeutic evaluation.