Vascular organoids: unveiling advantages, applications, challenges, and disease modelling strategies

Abstract

Understanding mechanisms and manifestations of cardiovascular risk factors, including diabetes, on vascular cells such as endothelial cells, pericytes, and vascular smooth muscle cells, remains elusive partly due to the lack of appropriate disease models. Therefore, here we explore different aspects for the development of advanced 3D in vitro disease models that recapitulate human blood vessel complications using patient-derived induced pluripotent stem cells, which retain the epigenetic, transcriptomic, and metabolic memory of their patient-of-origin. In this review, we highlight the superiority of 3D blood vessel organoids over conventional 2D cell culture systems for vascular research. We outline the key benefits of vascular organoids in both health and disease contexts and discuss the current challenges associated with organoid technology, providing potential solutions. Furthermore, we discuss the diverse applications of vascular organoids and emphasize the importance of incorporating all relevant cellular components in a 3D model to accurately recapitulate vascular pathophysiology. As a specific example, we present a comprehensive overview of diabetic vasculopathy, demonstrating how the interplay of different vascular cell types is critical for the successful modelling of complex disease processes in vitro. Finally, we propose a strategy for creating an organ-specific diabetic vasculopathy model, serving as a valuable template for modelling other types of vascular complications in cardiovascular diseases by incorporating disease-specific stressors and organotypic modifications. Graphical abstract

Melatonin alleviates myocardial dysfunction through inhibition of endothelial‐to‐mesenchymal transition via the NF‐κB pathway

“…43 VOs are proposed as a more physiopathological platform compared to tranditional animal models and 2D cell cultures. 44 3D organoids have the capability to simulate the inherent interactions in vascular symtem, including the diverse cells and the extracellular matrix, and to research into coordinated functions and hierarchical organization within a biomimetic microenvironment. 44,45 We have recently developed VOs to serve as a model for identifying certain disease processes and therapeutic molecules.…”

“…44 3D organoids have the capability to simulate the inherent interactions in vascular symtem, including the diverse cells and the extracellular matrix, and to research into coordinated functions and hierarchical organization within a biomimetic microenvironment. 44,45 We have recently developed VOs to serve as a model for identifying certain disease processes and therapeutic molecules. The current trend in new drug design involves the utilization of 3D organoids for discovering the effects of the drugs.…”

“…Previous studies have shown that VOs derived from human iPSCs served as a valuable model for drug screening to assess therapieutic effects 43 . VOs are proposed as a more physiopathological platform compared to tranditional animal models and 2D cell cultures 44 . 3D organoids have the capability to simulate the inherent interactions in vascular symtem, including the diverse cells and the extracellular matrix, and to research into coordinated functions and hierarchical organization within a biomimetic microenvironment 44,45 .…”

Current Insights into Tissue Injury of Giant Cell Arteritis: From Acute Inflammatory Responses towards Inappropriate Tissue Remodeling

“…Another proposed model for the construction of human arteries incorporating 3D bioprinting approaches was described by Xu et al This novel approach successfully produced vessels that closely mimic human medium-sized vessels but did not involve using immune cells to test this methodology in the setting of autoimmune disease research [ 232 ]. Moreover, patient-derived induced pluripotent stem cells are strongly suggested in constructing 3D in vitro models to retain the epigenetic, transcriptomic, and metabolic profile of the patient of origin [ 233 , 234 ]. The abovementioned efforts to construct bioengineered human arteries indicate that the ever-expanding tools and novel methodologies hold the potential for the generation of more physiologically relevant in vitro models of large vessel vasculitis in the foreseeable future.…”

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

“…What this also means is that patient-specific differences in disease susceptibility due to genetic background, for example the effect of accompanying SNPs, can be modelled in the absence of the confounding “main” mutation. Several studies have used iPSCs and derived vascular cells—VSMCs, pericytes and ECs—to model a variety of vascular diseases including, pulmonary arterial hypertension ( 112 – 119 ), Hutchison-Gilford progeria ( 120 – 124 ), atherosclerosis ( 47 , 125 , 126 ), neurodegenerative cerebro-vascular conditions like Moyamoya disease ( 127 – 131 ), CADASIL ( 132 – 135 ), diabetes and its associated conditions ( 136 – 138 ).…”