ZEANA SAMI HAMDONAH/THE VARSITY

A collaborative study by researchers in the US and Canada, including Dr. York P-C Pei and Dr. Xuewen Song from the Division of Nephrology at Toronto General Hospital, developed miniature kidneys to track the progression of polycystic kidney disease (PKD). The team was led by Dr. Benjamin Freedman of the University of Washington School of Medicine.

PKD is a genetic disorder that results in the formation of cysts, or fluid-filled sacs, in kidneys, which can eventually lead to loss of kidney function. Currently, there is no cure for PKD, and treatments are only targeted toward managing symptoms.

Combining stem cell biology with the gene editing tool CRISPR, the team created kidney organoids that resemble a human kidney from human stem cells. The goal was to better understand the pathobiology of PKD and pave the way for patient-specific treatments.

Organoids are miniature organs created in vitro, or outside of a living organism. In this study, kidney organoids were created from pluripotent stem cells capable of developing into any adult cell type. These pluripotent cells were able to mature into cells that structurally and functionally resembled those found in human kidneys.

Once these kidneys were created in a petri dish, the researchers used CRISPR technology to edit the DNA at specified points and modify certain genes. By mutating two genes, PKD1 and PKD2, the researchers were able to engineer kidney organoids that interfere with protein production and induce PKD.

This allowed the team to observe the early stages of cyst formation, known as cystogenesis, which characterizes PKD. Through observing the kidney organoids, they also discovered that proteins responsible for PKD can be influenced by their environment and that manipulating cell environment can provide a better understanding of how PKD progresses.

“[This] is telling us that looking at the outside environment of the kidney may be the key to curing the disease. This gives us a whole new interventional window,” said Freedman.

In Canada, PKD affects around one in every 500 people per year. Approximately half of the people with the type 1 autosomal dominant form of PKD will require kidney transplantation or dialysis by the age of 60.

The researchers hope to one day grow on demand new kidney tissue that is completely compatible with an individual’s body.

These organoids, with and without PKD gene mutations, have been shown to survive in mice. It remains to be determined whether or not kidney organoids can be used for transplantation in humans.

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