Controlling cellular plasticity to improve in vitro models for kidney regeneration

Given the increasing prevalence of end-stage kidney disease, the high morbidity and mortality of dialysis treatment, and the shortage of donor kidneys, the field of nephrology is progressively shifting its focus to regenerative medicine. In particular, both the development of a bioartificial kidney and the improvement of kidney-mimicking systems developed in vitro (e.g. organoids or tubuloids) for implantation purposes are attractive therapeutic strategies. However, a major hurdle to overcome with the current kidney cell models available is the limited control over cellular plasticity to augment cell-type-specific functionality. In this review, we summarize the main knowledge on important factors known to drive or affect maturation of kidney epithelial cells. This might aid in the advancement of in vitro kidney models to enable their use in regenerative medicine.