Before new drugs can be approved for use, they have to be put through rigorous safety tests on animals and artificial models, but the results don't always carry over to the human body. Miniature organs grown in labs have been helpful test subjects in the past, but the problem is that they don't replicate how drugs affect other parts of the body. Now, researchers at Wake Forest Institute for Regenerative Medicine have combined several of these organ models into one system, to create a more detailed "body-on-a-chip."
Mini brains, kidneys and hearts have all been grown in the lab, and in other cases, cells of various organs have been implanted onto chips to mimic their function. Called organs-on-chips, these systems are used to test the effectiveness and safety of drugs, as well as modeling diseases or lifestyle effects like smoking on certain cells. But testing on just one organ model at a time means the bigger picture is often missed.
"If you screen a drug in livers only, for example, you're never going to see a potential side effect to other organs," says Aleks Skardal, lead author of the study. "By using a multi-tissue organ-on-a-chip system, you can hopefully identify toxic side effects early in the drug development process, which could save lives as well as millions of dollars."
For their experiments, the Wake Forest researchers grew organoids – tiny three-dimensional versions of organs – of the heart, lungs and liver, and connected them together in a sealed system, complete with a nutrient-rich liquid to simulate blood flowing through it.
To test that the system accurately mimics known human function, the team first gave a toxic dose of a painkiller to the liver, and then another drug designed to combat those ill effects. Sure enough, the mini-organ responded as expected, to both the overdose and the treatment. Then, the researchers experimented with the whole body-on-a-chip to see how well it created a multi-organ response to drugs.
In one test, they gave the system a drug that's used to combat cancer, which has the unfortunate side effect of causing scarring of the lungs. That effect was seen, but the multi-tissue system revealed a previously unknown side effect as well: the beating of the heart sped up and then later stopped completely. The researchers attribute that effect to inflammatory proteins from the lungs circulating throughout the system.
"This was completely unexpected, but it's the type of side effect that can be discovered with this system in the drug development pipeline," says Skardal.
The next steps for the project are to increase the speed of the system, which will help the scientists scale it up for larger screenings, and then add more organs to the "body."
"Eventually we expect to demonstrate the utility of a body-on-a-chip system containing many of the key functional organs in the human body," says Anthony Atala, senior researcher on the project. "This system has the potential for advanced drug screening and also to be used in personalized medicine – to help predict an individual patient's response to treatment."
The research was published in the journal Scientific Reports.
