Navigating Vascular Complexity: Insights From hiPSC-derived vascular cells to Advanced 3D Models

The research collected in this thesis focusses on the vascular system, emphasizing its heterogeneity and complexity in both health and disease. It argues for tailored approaches in vascular replacement, pre-vascularization strategies, and disease modeling.

The first part centers on the use of human induced pluripotent stem cell (hiPSC)-derived vascular cells for tissue engineering and disease modeling. The main cell source used in this thesis are cells derived from hiPSC-derived blood vessel organoids. We hypothesized that vascular organoid derived cells would be a suitable cell source for the development of various vascular (disease) models.

With multiple advanced in vitro techniques, we confirmed that these cells offer a versatile platform for both micro- and macrovascular regeneration. The chapters in this thesis dissect various aspects using vascular organoid derived cells. For example we induced and regulated fenestrations in hiPSC-derived endothelial cells and we compared the phenotypic switch in hiPSC-derived vascular smooth muscle cells to their natural counterparts. In parallel, the thesis explores the impact of mechanical stimuli in advanced 3D models, aiming to replicate physiological conditions accurately.

The thesis also investigates the impact of mechanical forces in vascular regulation and disease modeling. We introduce innovative approaches like a microfluidic chip to study vascular pathologies in vitro, particularly focusing on early-stage atherosclerosis. This model offers insights into vascular cell interactions under physiologically relevant conditions, a potential platform for drug testing and mechanistic studies.

Throughout this thesis, there's an aim towards animal-free alternatives for culture components, mainly including Matrigel, aligning with ethical and translational research goals. The ultimate aim is to bridge the gap between bench and bedside, leveraging hiPSC-derived cells for personalized regenerative therapies and disease interventions.

The studies in this thesis contain hiPSCs from healthy donors. Future prospects include the use of patient-derived cells, to be able to study vascular development in disease conditions. In addition, using patient-derived cells would open up the possibilities for the development of drug-screening platforms and individualized disease models.

In conclusion, the thesis underscores the potential of hiPSC-derived vascular cells in reshaping the landscape of vascular regeneration and disease modeling. It not only advances our understanding of vascular biology but also paves the way for innovative solutions in clinical practice, a step towards personalized medicine.