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

Abstract

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.