Part of the institute’s “Body on a Chip” project, the researchers hope to use the micro organs to mimic how the human body responds to medications. This could potentially help reduce the costs of developing new medications, which currently are tested on human cells and animals and cost pharmaceutical companies about $2 billion and have a 90% failure rate.
“There is an urgent need for improved systems to accurately predict the effects of drugs, chemicals, and biological agents on the human body,” says Anthony Atala, M.D., director of the institute and senior researcher on the Body on a Chip project, funded by the Defense Threat Reduction Agency.
According to the researchers, they have successfully engineered micro-sized 3D organs – known as organoids – and connected them together on a single platform to monitor their function. This, they say, is the first such success using 3D organ structures, which more accurately model the human body than organ cells.
The researchers used 3D printing and other methods to make the organ structures from cell types found in native human tissue. The organ types were chosen based on susceptibility to drug toxicity – i.e., heart and livers – and for being a point of entry for toxic elements – i.e., lungs.
The organoids were placed in a sealed, monitored system that includes a real-time camera. They were kept alive by a nutrient-filled liquid that circulates through the system and that was also used to introduce potential drugs into the system.
In testing the organoids with toxic drugs and mitigating treatments to ensure similarity to their human counterparts, the researchers found that the individual organoids accurately reflected the responses seen in human patients. However, even more important than how an individual organ responds to drugs, say the researchers, is how the body as a whole responds, as drugs often have unexpected toxic effects in tissues not directly targeted.
“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, Ph.D., assistant professor at Wake Forest Institute for Regenerative Medicine, and the lead author of a paper on the research. “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.”
In testing how well the body-on-a-chip system mimics a multi-organ response, the researchers found at least one scenario where a cancer drug introduced into the system unexpectedly affected the system’s heart, where a control experiment using only the heart showed no such response. It is this type of side effect, say the researchers, that can be discovered with this system in the drug development pipeline.
“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 Atala. “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.”