Kidney organoids that aggregate in response to developmental cues have been generated from embryonic and induced pluripotent stem cells (PSCs). Using a modified protocol originally developed for the expansion of adult intestinal stem cells, researchers now show that kidney tubular epithelial organoids can be established from kidney tissue, as well as from urine. These so-called tubuloids can be used to model infectious, malignant and genetic kidney diseases. “The ability to culture tubular epithelium in this way is in line with the fact that adult stem cell-derived organoids recapitulate organ regeneration rather than development: tubule epithelium readily regenerates in vivo, whereas glomeruli do not regenerate easily,” explains Frans Schutgens. “This system complements PSC-derived organoids, which model development and therefore include glomeruli.”

To establish tubuloids the researchers used digested tubular fragments from human and mouse kidney. The tubuloids could be maintained in culture for >6 months and demonstrated chromosomal stability. Gene expression analysis showed that the tubuloids predominantly expressed markers of proximal tubule cells, but cells representative of collecting duct and loop of Henle cells were also present.

The researchers then used tubuloids to model three kidney diseases. Infection of the tubuloids with BK virus induced enlargement of tubuloid nuclei, typical of BK virus nephropathy. Tubuloid infection was also induced by administration of infected urine. Tumour tubuloids were also established from two patients with Wilms tumour, and finally, tubuloids were established from the urine of a patient with cystic fibrosis, negating the need for nephrectomy or biopsy. Schutgens says that urine-derived tubuloids could represent an accessible approach to establish cultures from patients with tubular kidney diseases, while the ability to generate tubuloids from tumour and matching normal tissue will enhance understanding of different types of kidney cancer.