A team of researchers in Utrecht, Holland has successfully created kidney organoids in the lab from adult human stem cells that are capable of surviving for more than 6 months.
The researchers were able to successfully create the kidney organoids using adult stem cells taken from patients. This is the first time that kidney organoids have been created from adult stem cells, although mini kidneys have previously been created using induced pluripotent stem cells. In addition to creating cell cultures from stem cells, the researchers were able to create cultures from urine cells.
Analyses of the organoids using gene expression, immunofluorescence, and tubular functional studies confirmed they contained both proximal and distal nephron segments and displayed active (trans-)epithelial transport function.
While the organoids were very small and cell structures were simple, they shared many of the characteristics of real human kidneys and, as such, they can be used to study a range of kidney disorders, infections, and hereditary kidney diseases to determine exactly how they alter kidney function. The kidney organoids can also help scientists better understand how healthy kidneys function.
The researchers used their organoids to study model infectious and hereditary kidney diseases. They established organoids from Wilms tumors, a rare form of kidney cancer and the most common kidney cancer in children. They were also able to derive organoids from the urine of a patient with cystic fibrosis to study the effectiveness of treatment ex vivo. Patients who undergo kidney transplants are at risk of viral infections, for which there are no effective treatments. The researchers recreated a kidney viral infection using one of most common viruses that affect transplant patients. In all cases, the researchers were able to recreate phenomena that are seen in vivo.
“We can use these mini kidneys to model various disorders: hereditary kidney diseases, infections and cancer, which allows us to study in detail what exactly is going wrong”, said Hans Clevers, Professor of Molecular Genetics at the University Medical Center Utrecht and group leader at the Hubrecht Institute.
The research was conducted at the Regenerative Medicine Centre Utrecht and was a collaborative effort between researchers at the Hubrecht Institute, Princess Máxima Center, Utrecht University and University Medical Center Utrecht.
The research is detailed in the paper – Tubuloids derived from human adult kidney and urine for personalized disease modeling – which was recently published in the journal Nature Biotechnology. DOI: 10.1038/s41587-019-0048-8