“Body-on-a-chip” uses micro organs to test out new drugs
Scientists have engineered micro hearts, lungs and livers that can potentially be used to test new drugs.
A team at the North Carolina-based Wake Forest Institute for Regenerative Medicine believe that combining micro-organs in a monitored system will provide a sufficiently accurate representation of the human body that the effect of new medications can be analysed.
The goal of the effort, known as a “body-on-a-chip”, is to help reduce the estimated $2bn price tag and 90 per cent failure rate that pharmaceutical companies face when developing new medications.
Drug compounds are currently screened in the lab using human cells and then tested in animals. But neither of these methods adequately replicates how drugs affect human organs.
“There is an urgent need for improved systems to accurately predict the effects of drugs, chemicals and biological agents on the human body,” said Anthony Atala, director of the institute and senior researcher on project.
The research team have successfully engineering micro-sized 3D organs, known as organoids, and connecting them together on a single platform to monitor their function.
While other teams have combined cells from multiple organs in a similar system, this is the first reported success using 3D organ structures, known to be higher functioning and to more accurately model the human body.
The organ structures were made from cell types found in native human tissue using 3D printing and other methods.
Heart and livers were selected for the system because toxicity to these organs is a major reason for drug candidate failures and drug recalls. Lungs are the point of entry for toxic particles and also for aerosol drugs, such as asthma inhalers.
The organoids are placed in a sealed, monitored system - complete with real-time camera. A nutrient-filled liquid that circulates through the system keeps the organoids alive and is used to introduce potential drug therapies into the system.
The researchers first tested the organoids to ensure their similarity to human organs. For example, the micro-liver received a high dose of a common pain reliever - and then a different drug to counteract the toxic effects.
“The data shows a significant toxic response to the drug as well as mitigation by the treatment, accurately reflecting the responses seen in human patients,” said assistant professor Aleks Skardal.
But more important than how an individual organ responds to drugs is how the body as a whole responds. In many cases during testing of new drug candidates - and sometimes even after the drugs have been approved for use - drugs have unexpected toxic effects in tissues not directly targeted by the drugs themselves.
“If you screen a drug in livers only, for example, you’re never going to see a potential side effect to other organs,” said Skardal. “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.”