Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic stroke disorder, caused by mutations in NOTCH3. The capillaries and arterioles in CADASIL patients exhibit a reduced vascular mural cell (vMC) investment and damage to the endothelium. Current murine models fail to recapitulate the human phenotype, namely spontaneous stroke. Cell models rely on overexpression of the mutant NOTCH3, obscuring the effect caused by the NOTCH3 mutation due to the increased gene dose from the overexpression. This thesis describes the development of induced pluripotent stem cells (iPSCs) from CADASIL patient and the differentiation of the iPSCs to vascular mural cells (vMCs) and endothelial cells (ECs) to model the CADASIL vasculature in vitro. The iPSC system is advantageous over the conventional cell model in its ability to retain the genetic background of the patient and the NOTCH3 mutation without requiring additional genetic manipulation. The in vitro model revealed that the CADASIL iPSC-derived vMCs (iPSC-vMCs) exhibited an altered expression and secretion of vascular endothelial growth factor (VEGF-165) and epidermal growth factor (EGF). Using an in vitro angiogenesis assay, we observed a premature loss of CADASIL iPSC-vMCs from the endothelial tubule structure, leading to premature degradation of the structure. The reduced tubule stability was partially rescued by NOTCH3 siRNA knockdown, suggesting a gain-of-function mechanism for this specific phenotype. The CADASIL iPSC-vMCs also exhibited an increased sensitivity to apoptotic stress which was not restored by NOTCH3 siRNA knockdown, indicating the existence of different underlying mechanisms. In addition, the CADASIL iPSC-vMCs had a persistent contractile phenotype and a lower expression of the nitric oxide receptor GUCY1B3, required for vMC relaxation. The model described here reflects previous histological findings of vMCs loss from capillary structures, increases apoptosis of vMCs and endothelial damage in CADASIL patients. We have begun to elucidate the mechanisms by which the angiogenesis and vessel stability were altered and identify novel pathways been affected in CADASIL. Understanding the molecular mechanisms of this condition is pivotal in identification of therapeutic targets and developing future treatments. The established iPSC CADASIL model represents a valuable resource that could be further interrogated to understand cellular signalling involved in the interactions between vMCs and ECs in CADASIL, and the contribution of neurovascular interactions to CADASIL pathology by differentiating the patient-specific iPSCs into glial cells and neurones. The molecular insight discovered in CADASIL may be applied to elucidate the mechanisms of stroke biology in general, which could benefit stroke prevention in risk populations.