Human kidney organoids: progress and remaining challenges

Abstract

Kidney organoids are regarded as important tools with which to study the development of the normal and diseased human kidney. Since the first reports of human pluripotent stem cell-derived kidney organoids 5 years ago, kidney organoids have been successfully used to model glomerular and tubular diseases. In parallel, advances in single-cell RNA sequencing have led to identification of a variety of cell types in the organoids, and have shown these to be similar to, but more immature than, human kidney cells in vivo. Protocols for the in vitro expansion of stem cell-derived nephron progenitor cells (NPCs), as well as those for the selective induction of specific lineages, especially glomerular podocytes, have also been reported. Although most current organoids are based on the induction of NPCs, an induction protocol for ureteric buds (collecting duct precursors) has also been developed, and approaches to generate more complex kidney structures may soon be possible. Maturation of organoids is a major challenge, and more detailed analysis of the developing kidney at a single cell level is needed. Eventually, organotypic kidney structures equipped with nephrons, collecting ducts, ureters, stroma and vascular flow are required to generate transplantable kidneys; such attempts are in progress.