New Approach Used to Generate Functional Kidney Organoids for Research and Drug Screening

New Approach Used to Generate Functional Kidney Organoids for Research and Drug Screening

Image source: Zipeng Zeng/Li Lab, USC Keck School of Medicine.

USC researchers have created a key building block for assembling new types of synthetic kidney organoids to study kidney diseases and identify new treatments and regenerative approaches for patients.

The Keck School of Medicine researchers, led by Zhongwei Li, created rudimentary kidney structures from ureteric bud progenitor cells (UPCs), which play a key role in the early development of kidney tissue. Initially, the researchers harvested mouse UPCs and used a cocktail of molecules to encourage the cells to form uretic buds. During normal development, uretic buds form the collecting duct system in the kidney.

Following their success, the researchers showed the technique also works with human UPCs and they developed a different cocktail of molecules that they used to differentiate human stem cells into UPCs which went on to form ureteric bud organoids. The researchers demonstrated their method was reliable and allowed them to mature the ureteric bud organoids into complex collecting duct organoids.

The organoids created by the researchers could help scientists gain a better understanding of kidney development and disease and could be used for screening potential therapeutic drugs and developing new treatments for kidney disorders.

The methods used by the researchers could also play an important role in the development of synthetic kidneys. The researchers showed that when the ureteric bud organoids were combined with a population of nephron-forming mouse progenitor cells, an extensive branching network of tubes were formed that resembled the collecting duct system which was fused with rudimentary nephrons – the filtering parts of the kidney.

“Our engineered mouse kidney established a connection between nephron and collecting duct—an essential milestone towards building a functional organ in the future,” said Li.

The researchers can also use their techniques to create kidney organoids with gene mutations to model kidney abnormalities. To demonstrate this, the researchers knocked out a gene responsible for a group of abnormalities referred to as congenital abnormalities of the kidney and urinary tract (CAKUT) and created kidney organoids that could be used in the development of novel preventive, diagnostic, and therapeutic approaches for treating CAKUT and other kidney abnormalities, or even regenerating organs through cell or tissue replacement therapies.

You can read more about the study in the paper – Generation of patterned kidney organoids that recapitulate the adult kidney collecting duct system from expandable ureteric bud progenitors – which was recently published in Nature Communications. DOI: 10.1038/s41467-021-23911-5