Researchers at the Washington University School of Medicine have identified the presence of rogue cells in organoids and developed a method to prevent their formation.
Researchers at the Washington University School of Medicine (MO, USA) investigating treatments for kidney disease have developed a method to prevent rogue brain and muscle cells within kidney organoids. They hope the same approach could be adopted by other scientists who find unwanted cells in other organoids.
The researchers investigated two methods of growing kidney organoids — the first starting with embryonic stem cells and the other with induced pluripotent stem cells reprogrammed from adult cells. Then, using single cell RNA sequencing, the gene activity in 83,130 cells from 65 kidney organoids was analyzed by computer.
The results, published in Cell Stem Cell, found that 10—20% of the cells in the organoids had developed into brain and muscle cells instead of kidney cells, regardless of the growth method. By reconstructing each step in the process by which stem cells developed into brain and muscle cells, the scientists were able to accurately see the point at which things went off the rails and block the formation of rogue cells. Overall, this approach reduced the number of brain cells by 90% and could be used to assist other scientists eliminate rogue cells in other types of organoids.
“There’s a lot of enthusiasm for growing organoids as models for diseases that affect people,” explained Benjamin Humphreys, director of the Division of Nephrology, Washington University School of Medicine. “But scientists haven’t fully appreciated that some of the cells that make up those organoids may not mimic what we would find in people.”
“The good news is that with a simple intervention, we could block most of the rogue cells from growing. This should really accelerate our progress in making organoids better models for human kidney disease and drug discovery, and the same technique could be applied to targeting rogue cells in other organoids.”