Human blood vessel organoids as a model of diabetic vasculopathy

By Reiner A. Wimmer, Alexandra Leopoldi, Martin Aichinger, N. Wick, B. Hantusch, M. Novatchkova, Jasmin Taubenschmid, M. Hämmerle, Christopher Esk, J. Bagley and 10 more. Nature, 2019

690 citations recorded by the source corpus.

The increasing prevalence of diabetes has resulted in a global epidemic1. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and amputation of lower limbs. These are often caused by changes in blood vessels, such as the expansion of the basement membrane and a loss of vascular cells2–4. Diabetes also impairs the functions of endothelial cells5 and disturbs the communication between endothelial cells and pericytes6. How dysfunction of endothelial cells and/or pericytes leads to diabetic vasculopathy remains largely unknown. Here we report the development of self-organizing three-dimensional human blood vessel organoids from pluripotent stem cells. These human blood vessel organoids contain endothelial cells and pericytes that self-assemble into capillary networks that are enveloped by a basement membrane. Human blood vessel organoids transplanted into mice form a stable, perfused vascular tree, including arteries, arterioles and venules. Exposure of blood vessel organoids to hyperglycaemia and inflammatory cytokines in vitro induces thickening of the vascular basement membrane. Human blood vessels, exposed in vivo to a diabetic milieu in mice, also mimic the microvascular changes found in patients with diabetes. DLL4 and NOTCH3 were identified as key drivers of diabetic vasculopathy in human blood vessels. Therefore, organoids derived from human stem cells faithfully recapitulate the structure and function of human blood vessels and are amenable systems for modelling and identifying the regulators of diabetic vasculopathy, a disease that affects hundreds of millions of patients worldwide. Organoids derived from human stem cells recapitulate the structure and functions of human blood vessels, and can be used to model and identify regulators of diabetic vasculopathy.

Subfields: Biomedical Engineering, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c95adad325f114f8e93375d2409e23ed8ba506c5

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1. Yue Liu
2. Keji Chen
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4. Luqi Huang
5. Wenting Wang
6. Yanfei Liu
7. Shiwei Liu
8. Yiwen Li

Citations in the corpus

• Diabetic vascular diseases: molecular mechanisms and therapeutic strategies (2023, background): “New technologies such as induced pluripotent stem cells should be developed to enrich experimental findings of DPD and construct model human blood vessel organoids.(129) Multi-omic studies(471,472) should explore the pathogenesis of DPD.”
• Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 (2020, neutral): “Of note, these organoids closely resemble human capillaries with a lumen, CD31 endothelial lining, PDGFR pericyte coverage, as well as formation of a basal membrane (Wimmer et al., 2019).”