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

Urdaneta González, K.E. (2026)

Doctoral Thesis

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.

• Angiogenesis
• Organ-on-Chips
• Stem cells
• Microphysiological Systems
• Endothelial cells
• Disease Modelling
• Drug testing
• Perzonalized medicine

• All authors: Urdaneta González, K.E.
• Supervisor: Mummery, C.L.
• Co-supervisor: Orlova, V.V.
• Committee: Goumans, M.J.T.H.; Maagdenberg, A.M.J.M. van den; Passier, P.C.J.J.; Meer, A.D. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2026-02-17
• ISBN (print): 9789465370361
• Sponsorship: Financial support by The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW, #NNF21CC0073729), Netherlands Organ-on-Chip Initiative, an NWO Gravitation project funded by the Ministry of Education, Culture and Science of the government of the Netherlands (024.003.001); the Netherlands Organization for Health Research and Development (ZonMw): PTO 446002501, and the Stichting AVS Proefdiervrij (18.07.2024).