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Lab Kidney Reveals Secrets of Polycystic Kidney Disease

Lab Kidney Reveals Secrets of Polycystic Kidney Disease

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  • Polycystic kidney disease causes cysts to grow in the kidneys.
  • Cysts can cause kidney damage and kidney failure.
  • The micro-environment of the kidney plays a role in cyst formation.

Polycystic Kidney Disease (PKD)
Polycystic kidney disease (also called PKD) causes numerous cysts to grow in the kidneys. These cysts are filled with fluid. If too many cysts grow or if they get too big, the kidneys can become damaged. PKD cysts can slowly replace much of the kidneys, reducing kidney function and leading to kidney failure.

PKD runs in families. It is an inherited disorder that is passed from parents to children through genes.


Learning from Mini-kidneys in a Lab
Polycystic kidney disease affects 12 million people. Until recently, scientists have been unable to recreate the progression of this human disease in a laboratory setting.

By creating and manipulating mini-kidney organoids that contain a realistic micro-anatomy, researchers can now track the early stages of polycystic kidney disease. The organoids are grown from human stem cells.

Benjamin Freedman, assistant professor of medicine in the Division of Nephrology at the UW School of Medicine, and his team at the Kidney Research Institute, led these studies in conjunction with scientists at other institutions in the United States and Canada. Freedman and his group also are investigators at the UW Medicine Institute for Stem Cell and Regenerative Medicine

"Beforehand, we had shown that these organoids could form PKD-like cysts, but what's new here is that we've used the model to understand something fundamental about that disease," said Freedman.

As one example, the team found that PKD mini-kidneys grown in free-floating conditions formed hollow cysts that were very large. These cysts could easily be seen. In contrast, PKD mini-kidneys attached to plastic dishes stayed small.

According to Nelly Cruz, the lead author of the paper, other manipulations to the organoid also affect the progression of polycystic kidney disease.

The Outside Environment of the Kidney Can Cause Polycystic Kidney Disease (PKD)
The study reported that, polycystin proteins, which are causing the disease, are sensitive to their micro-environment. Therefore, changing the interaction of the kidney with its micro-environment is key to changing the course of the disease.

By substituting certain physical components in the organoid environment, cyst formation can be increased or decreased.

The research team discuss how podocytes, which are specialized cells in the body that filter blood plasma to form urine, can be generated and tracked in a lab environment. Study of gene-edited human kidney organoids showed how podocytes form certain filtration barriers, called slit diaphragms, just as they do in the womb. This might give the team insight into how to counter the effects of congenital gene mutations that can cause glomerulosclerosis, another common cause of kidney failure.

This is an example of how medical scientists are making progress toward developing effective, personalized therapies for polycystic kidney disease and other kidney disorders.

"We need to understand how PKD works," Freedman said. "Otherwise, we have no hope of curing the disease."

"And our research," he added, "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.

References :
  1. Nelly M. Cruz, Xuewen Song, Stefan M. Czerniecki, Ramila E. Gulieva, Angela J. Churchill, Yong Kyun Kim, Kosuke Winston, Linh M. Tran, Marco A. Diaz, Hongxia Fu, Laura S. Finn, York Pei, Jonathan Himmerfard, Benjamin S. Freeman . Organoid Cystogenesis Reveals a Critical Role of Microenvironment in Human Polycystic Kidney Disease, Nature Materialshttp:dx.doi.org/10.1038/nmat4994

Source: Eurekalert

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