FROM UW MEDICINE TO THE INTERNATIONAL SPACE STATION: THE INCREDIBLE JOURNEY OF THE KIDNEYS ON CHIPS AND WHAT IT MEANS FOR LIFE ON EARTH
In February 2019, a 230 foot Falcon 9 Rocket will lift off from Cape Canaveral bound for the International Space Station with a cargo that includes 24 kidneys-on-chips: an emerging approach to disease research with far-reaching implications for the future of medicine – and space travel.
The orbital journey for these organs-on-chips is part of a multi-phase investigation that puts science on a fast track to new insights about the physiological nature of kidneys and has the potential to revolutionize the drug discovery process.
And, it might help us get ready for life on Mars. (More on that later.)
Rewriting the Book on Drug Discovery
The story begins here on Earth, where the drug discovery process is a slow, expensive process. Proving that a drug is safe and effective can take more than ten years and cost as much as $2 billion – and 90% of drugs fail in clinical trials. Early phases require extensive animal testing – a model that does not always accurately indicate how a drug will perform as it moves into human clinical trials.
Now, scientists from UW Medicine, Pharmacy and the Kidney Research Institute are developing tools that have the potential to rewrite the book on drug discovery. Organs-on-chips technology automates and accelerates trials, reduces the massive cost of R&D, and shifts the burden of testing from animals and humans to 3-dimensional models that mimic biological systems without actually being sentient. The key is being able to use technology to perform and repeat more tests, more rapidly, with more precise results.
“The power of this work is immense,” says Dr. Ed Kelly, Associate Professor of Pharmaceutics and ISCRM Faculty Member. “You’re actually doing clinical trials on chips and getting safety data before you’ve ever treated a person and you’re not relying on testing animals.”
Organs-on-chips are groupings of cells built to function just like human organs, only in a manufactured, 3-dimensional environment that can resemble a component belonging to a laptop computer. In this manmade arrangement, human-derived tissue and cells follow their natural marching orders in a fluid system, unaware of their ex-vivo status, while researchers gather data through controlled observations and experiments.
One team of UW Medicine researchers at ISCRM, led by Dr. Benjamin Freedman, Assistant Professor of Nephrology and ISCRM Faculty Member, is even putting human stem-cell derived kidney organoids onto chips. The organoids are miniature kidney structures that allow scientists to conduct clinical trials in a dish that could yield new treatments for disorders like polycystic kidney disease.
“We know that our organoids will show signs of polycystic kidney disease,” says Dr. Freedman. “That means we can use an organoid from a person as a surrogate for their own tissue, which opens up the possibility of testing drug responses much more efficiently than the existing clinical trial framework.”
For Dr. Kelly, opportunity knocked in 2016 when his NIH program officers encouraged his team to apply for a NASA initiative to send organs-on-chips into space. One year and one successful proposal later, the University of Washington is a part of a joint initiative with the National Center for Advancing Translational Sciences (NCATS), the Center for Advancing Science in Space (CASIS), and Bioserve Space Technologies, a center within the University of Colorado that specializes in bringing science into space.
The focus of the space-based investigation will be on the kidney, one of the organs that is essential for normal physiological homeostasis, from absorption and distribution to metabolism and excretion (or ADME). Studying Vitamin D metabolism, which happens in the kidney, could point to strategies for maintaining bone health on earth – or on long-term space voyages.
Why study kidney functioning in space?
“In the case of Vitamin D Metabolism,” explains Dr. Kelly, “We’re using the unique environment of the International Space Station to accelerate what happens in the kidney. In this case, we’re looking at the onset of osteoporosis, a huge, growing concern for our aging population. We can gather data about the disease much faster in microgravity than we could on the ground, which sheds light on new potential preventions and treatments for patients.”
And, of course, observing biological processes in kidneys on chips is much easier than studying kidneys belonging to busy astronauts, who are occupied by two hours of physical exercise per day just to offset the rapid bone loss that occurs in space. Meanwhile, on earth, Dr. Kelly’s team will be doing the same experiments on kidney tissue from the same donors, a one-G control that will produce a valuable set of comparative data.
New Frontiers for Mankind and Medicine
The use of organs-on-chips – on earth or in space – is opening a door to new possibilities for understanding and treating diseases that impact millions of people every year and may change the nature of drug discovery itself. In short, the terrestrial implications alone are eye-popping.
What comes next may be just as thrilling. Before long, more and more people will be traveling farther and farther into space. Plans are even in motion to send a manned mission to Mars. The dawn of commercial space travel will bring people with a much wider range of health profiles into microgravity environments. Understanding how these conditions affect, say, Vitamin D production, may point researchers to therapies that address problems like bone loss and kidney stones for astronauts – and, someday, civilian emigrants to Mars – during multiyear voyages in space.
And what is the role of stem cells in all this? In a word, scale.
For now, the cells going into orbit are primary cells from the tissues of patients whose kidneys were removed as part of treatment for renal cancer. The reason: in a limited study, using primary cells offers a more detailed picture of kidney functioning. But primary cells are like most cells in our bodies – they will only divide a certain number of times before dying.
According to Dr. Kelly, the future will belong to stem cells, which replicate indefinitely and can be programmed to become many different cell types. “For this technology to really have broader implications, particularly in the pharmaceutical industry, you need to have stem cells that you can actually use to populate a liver chip, a kidney chip, a brain chip, or an intestine chip – and do it over and over again.”
Indeed, the story of stem cells in space is about to take off. Now, stem cells from the University of Washington are headed into orbit on two missions over the next four years.