Researchers have developed an automated system that uses robots to rapidly produce human mini-organs from stem cells. The new system, developed by researchers at the University of Washington School of Medicine, could greatly expand the use of mini-organs in research and drug discovery.
Mini-organs, or organoids, have gained notoriety in recent years for their potential to advance biomedical research, but they can be painstaking to culture. In the current study, liquid-handling robots were used to introduce stem cells into plates that contained as many as 384 miniature wells, and then coaxed into turning into kidney organoids over a period of 21 days. Each microwell contained ten or more organoids, and each plate contained thousands of organoids.
"Ordinarily, just setting up an experiment of this magnitude would take a researcher all day, while the robot can do it in 20 minutes," said Benjamin Freedman, assistant professor of medicine, Division of Nephrology, at the UW School of Medicine, who led the research effort.
The robots were also trained to process and analyze the organoids using automated single cell RNA sequencing to identify all the cell types found in the organoids. The robots accurately characterized the cellular makeup of the kidney organoids, identifying the presence of both kidney and non-kidney cells.
The technique was also used to search for drugs that could affect disease. In one such experiment organoids were produced with mutations that cause polycystic kidney disease (PKD) and exposed to an array of substances. One such factor called blebbistatin that blocks myosin led to a significant increase in the number and size of cysts.
The findings were unexpected as myosin was not previously known to be involved in PKD, and additionally provided evidence that this system can be used to successfully screen for drug targets.
Details of the new technique and the team’s findings were published May 17 in Cell Stem Cell.
Image: This is a bird's eye view of a microwell plate containing kidney organoids, generated by liquid handling robots from human stem cells. Yellow boxed region is shown at higher magnification. Red, green, and yellow colors mark distinct segments of the kidney. Image courtesy of Freedman Lab/UW Medicine.