Self-assembly, buckling and density-invariant growth of three-dimensional vascular networks

Abstract

<jats:p>The experimental actualization of organoids modelling organs from brains to pancreases has revealed that much of the diverse morphologies of organs are emergent properties of simple intercellular ‘rules’ and not the result of top-down orchestration. In contrast to other organs, the initial plexus of the vascular system is formed by aggregation of cells in the process known as vasculogenesis. Here we study this self-assembling process of blood vessels in three dimensions through a set of simple rules that align intercellular apical–basal and planar cell polarity. We demonstrate that a fully connected network of tubes emerges above a critical initial density of cells. Through planar cell polarity, our model demonstrates convergent extension, and this polarity furthermore allows for both morphology-maintaining growth and growth-induced buckling. We compare this buckling with the special vasculature of the islets of Langerhans in the pancreas and suggest that the mechanism behind the vascular density-maintaining growth of these islets could be the result of growth-induced buckling.</jats:p>

Progress of organoid platform in cardiovascular research

“…At present, there have been successful vascular organoid self-assembly schemes [ 82 ]. Kirkegaard et al suggest that during vascular organoid self-assembly, the initial self-assembly of the closed structure is ensured by the correspondence of topic-bottom polarity (AB) to cell density, which is a crucial driver of lumen formation [ 83 ]. Cardiac organoid self-assembly requires the generation of cardiomyocytes (CMs), cardiac fibroblasts (CFs), and cardiac endothelial cells (ECs), the three main cell types in the heart, from hiPSC, and the combination of them into three-dimensional cardiac microtissues (MTs) [ 84 ].…”