How Putting Organs on Chips Could Revolutionize Medicine

Getting a new pharmaceutical from an idea in the chemistry lab to market takes many years and billions of dollars. Each year just several dozen new drugs are approved for use in the United States.

Human “organs-on-chips” are leading a revolution in drug safety testing. These devices use human cells to model the structure and function of human organs and tissues. By testing the potential effects of drugs on different organs faster than traditional methods, organs-on-chips can reduce the need for animal studies and better predict which new drugs will effectively treat human disease.

As part of an interdisciplinary research team, we’re working on a kidney-on-a-chip to improve our understanding of how kidney diseases begin and which drugs can safely treat them.

**********

Historically, laboratory testing for new drugs is performed in cells grown in dishes or flasks. If a drug passes initial screening tests in vitro, researchers next test it in vivo in live animals to determine the effects of a new drug on a whole system instead of just one cell type at a time. Finally, after many years of laboratory investigation, researchers will test a promising new drug in people to see if it is safe and effective.

The problem is 9 out of 10 of these drugs never make it from small-scale human tests to the patient because they turn out to be ineffective or toxic, even if they showed promising results in early testing.

Organs-on-chips have the potential to completely transform that system. Ranging from the size of a fingernail to that of a credit card, they’re composed of fluid channels and tiny chambers that contain human cell samples. Organs-on-chips in development in labs around the country include kidney, lung, liver, intestine, skin, brain, heart, bone and reproductive systems.

In an organ-on-a-chip, flowing liquid supplies the cells with oxygen and nutrients, similar to the way blood sustains cells in the human body. It’s this constant flow that makes these devices special. Cells grown in organs-on-chips devices act more like cells in a human organ than do cells grown in flat dishes without flow.

**********

Kidneys are incredibly important to overall human health. The two fist-sized kidneys remove drugs and unwanted compounds from the body and play a critical role in maintaining proper salt and water balance, blood pressure and vitamin D and bone health. Genetic conditions and even commonly administered medications can, in some circumstances, damage the kidneys.

In the U.S., 15 percent of adults have kidney diseases. But most don’t even know it, because kidney diseases often display no symptoms until the condition is very advanced. There’s a pressing need to understand how kidney disease begins, and to develop new safe and effective treatments.

Here at the University of Washington, our kidney-on-a-chip research team is composed of scientists from many different disciplines, including pharmacy, pharmaceutical sciences, nephrology (kidney medicine), toxicology, biochemistry and bioengineering.

In partnership with Nortis, Inc., a local biotechnology company, our team has created a small device — the size of a business card — with up to three tiny tubes, each one-thousandth the size of a drop of water, containing 5,000 human kidney cells. When tiny amounts of fluid are pumped through the tubes, the kidney cells are exposed to important signals that help the cells in the chip behave as if they were in a live kidney.

We’ve found that the kidney cells release signals – called biomarkers – of injury when exposed to known kidney toxins. Our research showed that cells on the chip released markers of injury commonly seen in the urine of people with kidney damage. Testing with the older method, using cells on plates, did not show any damage with the same treatment. This suggests that the kidney-on-a-chip may be better than existing methods at predicting if a new drug will cause kidney damage in humans.

This article was originally published on The Conversation.

Catherine Yeung, Research Assistant Professor of Pharmacy, University of Washington

Edward Kelly, Associate Professor of Pharmaceutics, University of Washington

Jonathan Himmelfarb, Director of the Kidney Research Institute and Professor of Medicine, University of Washington