Vascular cell and extracellular matrix interactions: implications for vascular regeneration and disease modeling

PhD thesis, Christian G. M. van Dijk

The human body depends on a specialized perfused blood vessel (vascular) network to provide all cells with oxygen and nutrients. Via the complex process of angiogenesis, formation of new small blood vessels from existing small blood vessels leads to the constant remodelling of this vascular network. This tightly regulated process highlights the complex interactions between vascular cells and their direct environment which are essential for blood vessel stability, -(pathological)development and -regeneration. A major challenge in regenerative medicine is the development of tissues with a functional vascular network to provide all cells with oxygen. Blood vessels can be mimicked in the laboratory, creating in vitro models. These models offer scientists the opportunity to unravel complex vascular interactions during development in health and disease.

The studies described in this thesis highlights the important interactions between two vascular cell types, the endothelial cell and the mural cell, in vascular development and vessel stabilization in health and disease. We attribute an important role of the direct (matrix) environment in regulating blood vessel and renal tubule development. These fundamental insights can be further implemented in diverse regenerative applications including the development of innovative and complex human in vitro vascular models. We also describe in this thesis the use of two models that focus on vascular research and better mimic the complex human environment. These models are clinically relevant by combining multiple characteristics of the complex vascular network, including relevant cell types and well-known risk factors, and provide the opportunity to study potential therapies. The implementation of these results leads to a better translation of research data to clinical applications.