From organoids to mini-organs: A case study in the kidney

Abstract Development of the permanent mammalian kidney, the metanephros, relies on complex reciprocal interactions between two nephrogenic cell populations; the branching ureteric bud and the metanephrogenic mesenchyme. Exploiting these interactions in vitro using murine renal progenitor cells allows the formation of self-organizing organoids of differing levels of complexity. Murine organoids made from dissociated progenitors can be used to probe mammalian kidney development and disease, including patterning, branching morphogenesis, gene function, developmental pathways, and small molecule screening. In addition, they can be used to develop techniques that may eventually lead to the creation of human renal transplant alternatives, model systems, or screening platforms for toxicology. The simplest of the murine organoids consists of a disorganized mix of immature nephrons and collecting ducts, whilst the more advanced organoids contain nephrons arranged around and connected to a single, radially symmetrical collecting duct system. Recently, we have taken another step forward by introducing a rudimentary urothelial trunk to the collecting duct system, whilst maintaining nephron development. Here, we review the field of murine renal organoids, and include a detailed protocol on how to generate them.