Creating a kidney organoid-vasculature interaction model using a novel organ-on-chip system

Abstract

Abstract Kidney organoids derived from human induced pluripotent stem cells (iPSCs) have proven to be a valuable tool to study kidney development and disease. However, the lack of vascularization of these organoids often leads to insufficient oxygen and nutrient supply. Vascularization has previously been achieved by implantation into animal models, however, the vasculature arises largely from animal host tissue. Our aim is to transition from an in vivo implantation model towards an in vitro model that fulfils the advantages of vascularization whilst being fully human-cell derived. Our chip system supported culturing of kidney organoids, which presented nephron structures. We also showed that organoids cultured on chip showed increased maturation of endothelial populations based on a colocalization analysis of endothelial markers. Moreover, we observed migration and proliferation of human umbilical vein endothelial cells (HUVECs) cultured in the channels of the chip inside the organoid tissue, where these HUVECs interconnected with endogenous endothelial cells and formed structures presenting an open lumen resembling vessels. Our results establish for the first-time vascularization of kidney organoids in HUVEC co-culture conditions using a microfluidic organ-on-chip. Our model therefore provides a useful insight into kidney organoid vascularization in vitro and presents a tool for further studies of kidney development and drug testing, both for research purposes and pre-clinical applications.