Generation of vascularized 3-dimensional (3D) kidney organoids from human pluripotent stem cells

Abstract

Human pluripotent stem cell (hPSC)-derived kidney organoids are revolutionizing the way we investigate renal physiopathology and development. However, intrinsic limitations such as efficiency and a lack of control over the cell types differentiating within, hamper their full utility. Here, we present the establishment of a highly efficient protocol for differentiating hPSCs into kidney organoids comprised of segmented nephrons, vasculature, and interstitial cells. By temporal modulation of canonical WNT-signalling, we could influence proximal-to- distal nephron patterning and the corresponding vasculature content. We identified a novel renal vascular progenitor that responds to podocyte-derived VEGF-A and mature into CD31+ endothelium. Following implantation into an immunocompromised host, kidney organoids rapidly engraft and undergo functional maturation as demonstrated by size-specific dextran filtration and the accumulation of putative filtrate within tubules. Our work represents an advanced version of kidney organoids that promise to offer extensive utility in both basic science and clinical practice.