Modeling vascular disease using self-assembling human induced pluripotent stem cell derivatives in 3D vessels-on-chip

Nahon, D.M. (2024)

Doctoral Thesis

Vascular diseases pose a significant burden on society, mainly due to the lack of effective treatment methods. A major reason for this is the shortcomings of current preclinical model systems. In this study, we have taken steps toward developing a more complex and relevant model system for (brain) blood vessels to address this issue. We used human induced pluripotent stem cells (hiPSCs) in the lab as a cellular source to generate the different types of cells needed for stable blood vessels. These cells were then combined in 3D microscopic culture environments (so-called vessel-on-chip systems) to closely mimic physiological conditions. Using this model, we were able to demonstrate specific abnormalities in a hereditary vascular disease, which was not possible with more 'traditional' culture methods. Additionally, we included brain cells to better investigate brain-specific disorders in the future. This work lays the essential foundation for a better understanding and treatment of complex vascular diseases, while potentially reducing the number of animal models needed.

• Organ-on-chip
• Vessel-on-chip
• Human induced pluripotent stem cells
• hiPSC-derived endothelial cells
• Disease modeling
• Hereditary hemorrhagic telangiectasia
• Blood-brain barrier
• BBB
• Microvascular networks
• Complex in vitro models

• All authors: Nahon, D.M.
• Supervisor: Mummery, C.L.
• Co-supervisor: Orlova, V.V.
• Committee: Goumans, M.J.T.H.; Maagdenberg, A.M.J.M. van den; Zonneveld, A.J. van; Hordijk, P.L.; Meer, A.D. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2024-06-26
• ISBN (print): 9789464961416
• Sponsorship: The Dutch Heart Foundation and Stichting Proefdiervrij