Advances and continuing challenges in differentiation of stem cells to human kidney tissue.

The capacity to generate a human model of the kidney via the directed differentiation of human pluripotent stem cells is a remarkable advance. Such three-dimensional multicellular tissues can accurately recapitulate certain kidney disease phenotypes in vitro, enabling the development of novel therapies for inherited kidney disease. These models also suggest the future possibility of engineering kidney tissue for kidney replacement therapy. Here, we focus on the latest advances in the field, including protocols for generating ureteric organoids and their combination with nephron-forming organoids to create integrated assembloid models, as well as examining the challenges in the application of these protocols. Although current protocols are modelled on differentiation in vivo, gaps in this knowledge remain, as well as challenges in recapitulating such complex events in vitro. The scale and complexity of the transcriptional analyses required to evaluate these models can also prove difficult to interpret. The genuine application of stem-cell-derived kidney tissue will require a deep understanding of what cells should not be present, what cell types are missing, how to increase the level of maturity of the component cells and whether organoids can reach a degree of maturation that can replicate postnatal kidney disease. Finally, the development of cellular therapies will require quality-controlled protocols to ensure both safety and efficacy.