Expansion of Human iPSC-Derived Ureteric Bud Organoids with Repeated Branching Potential

Abstract

Ureteric bud (UB) is the embryonic kidney progenitor tissue that gives rise to the collecting duct and lower urinary tract. UB-like structures generated from human pluripotent stem cells by previously reported methods show limited developmental ability and limited branching. Here we report a method to generate UB organoids that possess epithelial polarity and tubular lumen and repeat branching morphogenesis. We also succeed in monitoring UB tip cells by utilizing the ability of tip cells to uptake very-low-density lipoprotein, cryopreserving UB progenitor cells, and expanding UB tip cells that can reconstitute the organoids and differentiate into collecting duct progenitors. Moreover, we successfully reproduce some phenotypes of multicystic dysplastic kidney (MCDK) using the UB organoids. These methods will help elucidate the developmental mechanisms of UB branching and develop a selective differentiation method for collecting duct cells, contributing to the creation of disease models for congenital renal abnormalities.