Novel kidney organoid recapitulating the patterned distribution of principal cells (red) and intercalated cells (green) of an adult kidney’s collecting duct system. Credit: Zipeng Zeng/Li Lab
A group of scientists at USC’s Keck School of Medicine have developed a component that can be used to put together a synthetic kidney. In a recent study published in Nature Communications, Zhongwei Li and colleagues detail how they can create rudimentary kidney structures, known as organoids, that resemble the collecting duct system, which helps regulate the body’s fluid and pH balance by concentrating and transporting urine.
“Our progress in creating new types of kidney organoids provides powerful tools for not only understanding development and disease, but also finding new treatments and regenerative approaches for patients,” said Li, the study’s corresponding author and an assistant professor of medicine, and of stem cell biology and regenerative medicine.
The study’s lead authors, Ph.D. student Zipeng Zeng and postdoc Biao Huang, and their colleagues started with a population of ureteric bud progenitor cells, or UPCs, which play a crucial role in kidney formation in the early stages.
The scientists were able to generate combinations of chemicals that induce the cells to create organoids resembling uretic buds—the branching tubes that eventually give rise to the collecting duct system—by using mouse and then human UPCs. The researchers also discovered a new cocktail that can drive human stem cells to grow into ureteric bud organoids.
A different molecular cocktail induced ureteric bud organoids (made from mouse UPCs or human stem cells) to evolve into more mature and sophisticated collecting duct organoids.
The human and mouse ureteric bud organoids may also be genetically modified to carry disease-causing mutations, making them better models for understanding kidney disease and evaluating possible therapeutic medicines. The scientists, for example, knocked out a gene to produce CAKUT, an organoid model of congenital abnormalities of the kidney and urinary system.
In addition to acting as disease models, ureteric bud organoids may prove to be an important component in the development of a synthetic kidney. The researchers mixed mouse ureteric bud organoids with a second population of mouse cells to investigate this possibility: progenitor cells that become nephrons, the kidney’s filtering units. After placing the tip of a lab-grown ureteric bud into a cluster of NPCs, the scientists witnessed the development of an enormous network of branching tubes resembling a collecting duct system, united with rudimentary nephrons.