Modeling vascular inflammation with immune cell-vessel crosstalk in hiPSC-derived 3D vessels-on-chip

Bulut, M. (2025)

Doctoral Thesis

Vascular inflammation plays a central role in both homeostasis and disease, yet modeling its complexity in human systems remains challenging. This thesis presents advanced 3D vessel-on-chip (VoC) platforms using human induced pluripotent stem cell (hiPSC)-derived endothelial and mural cells, monocytes, and macrophages to investigate immune-vascular interactions. The work integrates physiological shear stress and multicellular co-culture to mimic the human microvasculature and assess inflammatory responses.
Two distinct VoC models were developed: one featuring single-lumen geometry to study endothelial barrier function and leukocyte transmigration, and another self-assembling model to explore microvascular network formation and perivascular macrophage function. These platforms enabled the investigation of leukocyte behavior in both healthy and disease contexts, including Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), a rare vascular disorder. The models revealed insights into how inflammatory triggers and patient-specific immune cells contribute to disease phenotypes.
This work highlights the potential of combining hiPSC technology and microfluidic engineering to model vascular inflammation in a human-relevant context. It lays the groundwork for more predictive disease modeling, drug screening, and personalized medicine applications.

• Vessel-on-chip
• Vascular inflammation
• Human induced pluripotent stem cells
• Endothelial cells
• Mural cells
• Microfluidics
• Leukocyte transmigration
• Hereditary hemorrhagic telangiectasia
• Perivascular macrophages
• Stem cell disease modeling

• All authors: Bulut, M.
• Supervisor: Mummery, C.L.
• Co-supervisor: Orlova, V.V.
• Committee: Hiemstra, P.S.; Goumans, M.J.T.H.; Lebrin, F.P.G.; Hordijk, P.L.; Meer, A.D. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2025-07-02
• ISBN (print): 9789465223797
• Sponsorship: Stichting Proefdiervrij