Blood Vessel Organoids for Development and Disease

Abstract

Despite enormous advances, cardiovascular disorders are still a major threat to global health and are responsible for one-third of deaths worldwide. Research for new therapeutics and the investigation of their effects on vascular parameters is often limited by species-specific pathways and a lack of high-throughput methods. The complex 3-dimensional environment of blood vessels, intricate cellular crosstalks, and organ-specific architectures further complicate the quest for a faithful human in vitro model. The development of novel organoid models of various tissues such as brain, gut, and kidney signified a leap for the field of personalized medicine and disease research. By utilizing either embryonic- or patient-derived stem cells, different developmental and pathological mechanisms can be modeled and investigated in a controlled in vitro environment. We have recently developed self-organizing human capillary blood vessel organoids that recapitulate key processes of vasculogenesis, angiogenesis, and diabetic vasculopathy. Since then, this organoid system has been utilized as a model for other disease processes, refined, and adapted for organ specificity. In this review, we will discuss novel and alternative approaches to blood vessel engineering and explore the cellular identity of engineered blood vessels in comparison to in vivo vasculature. Future perspectives and the therapeutic potential of blood vessel organoids will be discussed.

The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish

“…To date, blood vessel organoids have been widely used in disease modeling (e.g., diabetic vasculopathy, COVID-19) [ 111 , 160 , 163 , 164 ]. Moreover, the multicellular feature of vessel organoids makes them a valuable tool for investigating the mechanisms of diseases [ 165 ]. For instance, one study demonstrated that SARS-CoV-2 can directly infect kidney and blood vessel organoids and the infection can be prevented by soluble recombinant human ACE2 (hrsACE2) antibodies, although which specific cell types are susceptible to SARS-CoV-2 infection remains unclear [ 163 ].…”

Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: a comprehensive review

“…Organoid technology has become increasingly important, especially for secondary prevention of T2DM [ 216 ]. Recent advances include human capillary vascular organoids, human islet-like organoids and engineered islets from stem cells, which offer promising avenues for diabetes research [ 217 – 219 ]. As research advances, we expect the creation of in vitro systems capable of simulating specific organ ECs.…”

Engineering Organ-on-a-Chip Systems for Vascular Diseases

“…63,69,70 Blood vessel organoids that can self-organize and reproduce angiogenesis have also been used as a model for disease processes in specific organs. 71 OOCs were also used to demonstrate the impact of interstitial flow on vasculogenesis and pathological angiogenesis. 63 In the design, ECs and stromal fibroblasts were cocultured to form a microvascular network with neovessel sprouting and angiogenic remodeling in response to interstitial flow (Figure 2C).…”

“…Due to space limitations, we only mention a few representative examples here and invite readers to consult recent reviews on the topic. 7,11,71,113,114 Vascularized tumors on chip, particularly, have recently gained much attention, demonstrating the efficacy of OOCs for such complex interactions. 69,104,115 For instance, Heinrich et al 41 utilized a multilayered vascularized OOC model of pancreatic cancer to investigate fibrosis-induced compression of vasculature.…”