Human blood vessel organoids as a model of diabetic vasculopathy

Abstract

The prevalence of diabetes is increasing constantly, resulting in a global epidemic 1 . Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke or lower limb amputation; in large parts because of marked changes in blood vessels, defined by expansion of the basement membrane and a loss of vascular cells [2][3][4] . Diabetes also impairs endothelial cell (EC) function 5 and disturbs EC-pericyte communication 6 . How endothelial/pericyte dysfunction leads to diabetic vasculopathy remains largely elusive. Here we report the development of self-organizing 3D human blood vessel organoids from pluripotent stem cells. These human blood vessel organoids contain endothelial cells and pericytes that self-assemble into capillary networks 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 hyperglycemia and inflammatory cytokines in vitro induced thickening of the vascular basement membrane. Human blood vessels, exposed in vivo to a diabetic milieu in mice, also mimick the microvascular changes in diabetic patients. Dll4-Notch3 were identified as key

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

“…The pericyte represents a cell type of particular therapeutic interest, given its critical role in controlling BBB integrity via regulation of endothelial barrier function. Although not perfect mimics of the in vivo situation, organoid-based in vitro BBB systems for endothelium-pericyte interactions have recently been developed [171,172]. Pericytes exhibit plasticity after experimental injury [169], supporting the notion that their function may be improved or restored in an injury situation.…”

Xenograft and organoid model systems in cancer research

“…In an effort to model diabetic vasculopathy in vitro , a recent study reported the development of human blood vessel organoids from pluripotent stem cells that self‐assemble into capillary networks, containing endothelial cells and pericytes, surrounded by a basement membrane. Upon transplantation of these organoids into mice, a perfused vascular tree is formed, including arteries, arterioles and venules (Wimmer et al , ). These human blood vessel organoids may open new doors for PDTO co‐cultures.…”

Oxygen and nutrient delivery in tissue engineering: Approaches to graft vascularization

“…The graft will be better adapted to instantaneous perfusion, which in turn establishes a continued nutrient and oxygen delivery to the cells. Beyond this, newly emerging approaches, such as vascular organoids (Wimmer et al, 2019), may not only help us study vascularization in graft models but also potentially help establish a better graft vasculature. In conclusion, efforts should be made to integrate the currently available approaches by combining their strengths and eliminating their weaknesses.…”