WINSTON-SALEM, NC, Oct. 5, 2017 - Using the same expertise they've employed to build new organs for patients, scientists at Wake Forest Institute for Regenerative Medicine and colleagues have engineered micro hearts, lungs and livers that can potentially be used to test new drugs. By combining the micro-organs in a monitored system, the researchers aim to mimic how the human body responds to medications.

The goal of the effort, known as a "body-on-a-chip," is to help reduce the estimated $2 billion price tag and 90 percent 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, M.D., director of the institute and senior researcher on the multi-institution body on a chip project, funded by the Defense Threat Reduction Agency.
In Scientific Reports, published by Nature, the research team reports success 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 Aleks Skardal, Ph.D., assistant professor at Wake Forest Institute for Regenerative Medicine, who represented the multi-investigator team as the lead author of the paper.

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