Join us in this episode as we host Dr. McCracken, a leading figure in kidney regenerative medicine. Dr. McCracken shares his team's remarkable findings in the directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia, which is a pivotal step in the field of kidney regenerative medicine.

We begin our discussion by understanding how hPSCs are induced into pronephric progenitor cells with a 90% efficiency rate. These cells are then aggregated into spheres that closely resemble the molecular signature of the nephric duct. Within a three-dimensional matrix, these spheres develop into ureteric bud (UB) organoids that exhibit similar branching morphogenesis to the fetal UB and correct distal tip localization of RET expression.

Dr. McCracken explains how the cells derived from these organoids successfully incorporate into the UB tips in chimeric fetal kidney explant culture. In the later stages, UB organoids differentiate into CD organoids, which contain more than 95% CD cell types, as estimated by single-cell RNA sequencing.

Impressively, the CD epithelia demonstrate renal electrophysiologic functions, including ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells.

Through our conversation with Dr. McCracken, listeners will gain a deeper understanding of this groundbreaking research and its implications for kidney regenerative medicine.

Keywords: Kidney Regenerative Medicine, Human Pluripotent Stem Cells, hPSCs, Ureteric Bud, UB Organoids, Collecting Duct, CD Epithelia, Nephric Duct, ENaC, FOXI1.

McCracken, et al. Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types. 2022 https://doi.org/10.1038/s41587-022-01429-5