Mini-kidneys grown in lab reveal renal disease secrets

October 2, 2017
Kidney organoids grown in the lab and suspended in a lab dish show the formation of cysts (right) in the disease model of polycystic kidney disease. Normal kidney organoids are on the left. Credit: Freedman Lab/UW Medicine

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

Polycystic affects 12 million people. Until recently, scientists have been unable to recreate the progression of this human disease in a laboratory setting.

That scientific obstacle is being overcome. A report coming out next week shows that, by substituting certain physical components in the organoid environment, cyst formation can be increased or decreased.

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

They outlined their methods and results in a paper to be published Oct. 2 in Nature Materials

"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.

The video will load shortly.
Benjamin Freedman of UW Medicine in Seattle talks about his recent study using mini-kidney organoids to understand the progression of polycystic kidney disease. The video includes close ups of the organoids and cyst formation and other footage from his lab. Credit: Randy Carnell and Megan Clark/UW Medicine

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 .

"We've discovered that polycystin proteins, which are causing the disease, are sensitive to their micro-environment," she explained. "Therefore, if we can change the way they interact or what they are experiencing on the outside of the cell, we might actually be able to change the course of the disease." Cruz is a research scientist in the Freedman lab.

In another paper to be published in Stem Cells, Freedman and his 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.

The video will load shortly.
Watch kidney organoids grow from human cells and form cysts. These organoids were created as a disease model for polycystic kidney disease. Credit: Freedman lab/UW Medicine

Taken together, these papers are examples 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.

Explore further: Method to create kidney organoids from patient cells provides insights on kidney disease

More information: Nature Materials (2017). Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease, nature.com/articles/doi:10.1038/nmat4994

Related Stories

Method to create kidney organoids from patient cells provides insights on kidney disease

November 17, 2016
A new method to create kidney organoids from patient cells may provide insights into how kidney diseases arise and how they should be treated. The research will be presented at ASN Kidney Week 2016 November 15¬-20 at McCormick ...

Mini-kidney organoids re-create disease in lab dishes

October 23, 2015
Mini-kidney organoids have now been grown in a laboratory by using genome editing to re-create human kidney disease in petri dishes.

Study finds four genes linked to cystic diseases of the liver and kidney

April 6, 2017
Yale researchers are studying kidney and liver diseases to determine which genes are involved in the formation of cysts.

Surprising mechanism discovered in polycystic kidney disease

July 29, 2013
A study by Yale researchers has uncovered a new and unexpected molecular mechanism in the development of polycystic kidney disease, or PKD. The study appears in Nature Genetics.

CRISPR/Cas9 + HPSC = human PKD lab model

December 11, 2015
CRISPR/Cas9 is hot. News of the revolutionary gene editing technique that is already shaking up bioscience has finally reached the news media and the public. Now comes a first rate example of how CRISPR is changing the pace ...

Research findings point to new therapeutic approach for common cause of kidney failure

September 5, 2013
New research has uncovered a process that is defective in patients with autosomal dominant polycystic kidney disease, a common cause of kidney failure. The findings, which appear in an upcoming issue of the Journal of the ...

Recommended for you

Long-lasting blood vessel repair in animals via stem cells

October 23, 2017
Stem cell researchers at Emory University School of Medicine have made an advance toward having a long-lasting "repair caulk" for blood vessels. The research could form the basis of a treatment for peripheral artery disease, ...

Study reveals connection between microbiome and autoimmune disorders

October 23, 2017
Many people associate the word "bacteria" with something dirty and disgusting. Dr. Pere Santamaria disagrees. Called the microbiome, the bacteria in our bodies have all kinds of positive effects on our health, Santamaria ...

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.