1 in 600 people world-wide are diagnosed with polycystic kidney disease (PKD), which leads to reduced kidney function over time. A cure for PKD is not currently available, making it important that we find more effective therapies for this disorder. Our laboratory has successfully used pluripotent stem cells to generate kidney organoids that functionally model the physiology of the kidney. The goal of this study is to generate induced-pluripotent stem (iPS) cells, adult somatic cells which have been reprogrammed to an undifferentiated state, from individuals affected with PKD. The first step of the process is the isolation of the patient’s cells from hair and urine samples. We are then able to reprogram these disease-affected cells into iPS cells and later differentiate them into kidney cells to create a better model for the disorder and screen for novel drugs. The information we learn from this study will help us better understand how PKD progresses and improve its treatment. We also hope that one day we will be able to transplant healthy kidney cells back into their patients, eventually eradicating the need for kidney transplants.

More than 20 million Americans have some level of chronic kidney disease. With the constant deterioration of kidney function, treatments for this disease are in high demand. The only treatments available today include dialysis and kidney replacement. Unfortunately, these methods are not ideal due to a high dependency on the dialysis machine, long waiting lists, and possible rejection of the organ. Recently, protocols were developed that allow us to use pluripotent stem cells to generate kidney-like organoids. These organoids contain major structures of the nephron, the functional units of the kidney, which clean and filter the blood. For instance, podocytes, proximal tubules, distal tubules, and various cell types develop in these samples. This complexity that develops allows more accurate modeling of kidney disease than previous methods. A new protocol developed by our lab allows us to grow miniature organoids in microwells; this will allow us to perform large scale drug screens to search for treatments for various types of kidney disease. The miniature organoids were tested to see if they replicate the complexity seen in larger wells. Immunofluorescence was used to characterize the kidney organoids and the different cell types present within them. Additionally, proteins with the capability to perform biological functions, such as transporting glucose and other ions, are able to be studied as well. The results were compared to human fetal kidney tissue. The miniature organoids replicate all of the same structures found in the larger wells. Because of the strong similarities between miniature kidney organoids and the human kidney, they are optimal for drug testing. Impacts associated with new therapies will be easier to monitor through the miniature kidney models.