Getting a modern pharmaceutical from an approach in the chemistry lab to the market takes many years and billions of dollars. Each time just a dozen new drugs are approved for treatment in the United States.
Human “organs-on-chips” are starting a change in a medicine safety inspection. These methods use human cells to model the structure and purpose of human organs and tissues.
By examining the possible consequences of drugs on various organs quicker than conventional methods, organs-on-chips can reduce the need for animal thoughts and better predict which new drugs will treat human illness.
As part of an interdisciplinary study team with funding assistance from the National Center for Advancing Translational Sciences, 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.
Quicker And Better Testing
Historically, laboratory testing for new medicines is conducted in cells grown in dishes or flasks. If a medication passes initial screening tests in vitro, investigators next test it in vivo in live animals to manage the results 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 likely new medicine into people to see if it is safe and efficient.
The dilemma is 9 out of 10 of these drugs never make it from small-scale human experiments to the patient because they turn out to be incompetent or toxic, even if they showed encouraging results in early testing.
Organs-on-chips have the potential to change that system uniquely. Ranging from the size of a fingernail to that of a credit card, they’re composed of fluid channels and tiny cells that contain individual cell units. Organs-on-chips in development in labs around the country include kidney, lung, liver, intestine, skin, brain, heart, bone, and reproductive arrangements.
In an organ-on-a-chip, they are moving liquid stores the cells with oxygen and nutrients, related to the way blood provides cells in the human body. It’s this continuous flow that advances these means unique. Cells grown in organs-on-chips methods act more like cells in a human organ than do cells grown in flat plates without flow.
Fluid flows through a kidney-on-a-chip. Alex Levine, CC BY-ND
The Kidney-On-A-Chip
Kidneys are incredibly important to overall human health. The two fist-sized kidneys eliminate medications and unwanted compounds from the body and play a significant role in keeping proper salt and water balance, blood stress, and vitamin D and bone health. Genetic conditions and even regularly administered medicines can, in some circumstances, damage the kidneys.
In the U.S., 15 percent of adults have kidney diseases. But most don’t even remember it, because kidney conditions often display no symptoms until the situation is complicated. There’s a pressing need to understand how kidney condition begins and to develop new safe and effective treatments.
Here at the University of Washington, our kidney-on-a-chip investigation team is comprised of scientists from many diverse disciplines, including pharmacy, pharmaceutical sciences, nephrology (kidney medicine), toxicology, biochemistry, and bioengineering.
In conjunction with Nortis, Inc., a local biotechnology company, our team has produced a little device — the area of a business card — with up to three tiny tubes, each one-thousandth the size of a drop of water, including 5,000 human kidney cells. When small amounts of fluid are pumped through the tunnels, the kidney cells are exposed to essential signals that help the cells in the chip behave as if they were in a live kidney.
We’ve noticed that the kidney cells discharge signals – described biomarkers – of injury when shown to known kidney toxins. Our study showed that cells on the chip delivered markers of damage generally seen in the urine of people with kidney impairment. Testing with the older method, using cells on plates, did not show any loss in the same manner.
This implies that the kidney-on-a-chip may be better than existing methods at predicting if a new drug will cause kidney damage in humans.
These things do a better job of testing how molecules affect living human cells. Alex Levine, CC BY-ND
Connecting Organs-On-Chips
Now that we’ve had these encouraging results, innovative teams across the country are starting to compare different organs to replicate a more intricate, multi-organ system to give more critical insights into how drugs affect people.
For instance, we were able to join a liver-on-a-chip to a kidney-on-a-chip to learn how a plant variety used in some herbal medicines, called aristolochic acid, destroys kidney cells. This chip-to-chip investigation strengthens the need for interconnected organs-on-a-chip to replicate the affected workers in the human body.
In the coming year, our kidney-on-a-chip design will be one of many sent to the International Space Station, where low gravity races up differences in cells, seldom causing health problems for astronauts. The Space Station could be the perfect place to find out more about kidney diseases in weeks, rather than years or decades.
Organs-on-chips can also be practiced to discover new drug targets. Our team is assessing the kidney-on-a-chip as a tool to personalize medication selection and dosing in people with kidney cancer, polycystic kidney disorder, and chronic kidney illness.
Other organs-on-chips labs around the country are investigating diseases of the free system, brain, lungs, heart, and blood vessels. By working together, dozens of investigation teams are developing this new technology to revolutionize drug discovery, leading to the development of better and safer medications for all.
