Evidence for early kidney vasculature development by vasculogenesis and angiogenesis based on advanced in vivo chimeric model and depletion of CD31+/CD146+ intrinsic endothelial progenitors

Abstract

Kidney diseases are a significant health concern worldwide, with a growing demand for fundamental treatments, such as generation of transplantable organs from programmed cells. The generation of kidney organoids has led to significant advances in disease modeling. However, failure to establish a robust endothelial vasculature network in kidney organoids remains a barrier to oxygen support and gas exchange in renal tissue engineering. We targeted the development of early kidney vasculature system by advancing the classic mouse embryonic kidney organ culture and organoid model system by introducing a novel mini reservoir setup. The method improved integration with the highly vascularized chicken Chorion Allantois Membrane (CAM), enabling host blood flow to developing kidney organoids. We examined the origin and role of the CD31+ endothelial cells (ECs) and their CD146+ progenitors by applying a dissociated embryonic kidney approach. This enabled selected depletion of specific cell populations, followed by regeneration of the kidney organ primordia by reaggregation and placement on the CAM to assess organogenesis. The cell lineage and fate tracing with constitutively labelled cells revealed that the intrinsic endothelial CD146+ progenitor and those of CD31+ ECs in the kidney initiating organogenesis established the kidney vasculature. If the intrinsic EC progenitors were depleted, the mouse glomerular vascularization was rescued by the CAM derived ECs.