Screening of medicines on a chip

Researchers at the Wake Forest Institute of Regenerative Medicine, working under the guidance of Dr. Anthony Atala, have created miniature models of organs – the heart, lungs and liver – with the help of tissue engineering methods, potentially suitable for testing new drugs. They plan to combine these micro-organs in the form of a monitored system that reproduces the reactions of the human body to drugs.

The goal of this research area dedicated to the creation of the so-called "organism-on-a-chip" is to reduce the huge financial costs and the percentage of failures that pharmaceutical companies face when developing new drugs. Currently, experimental drugs are screened in the laboratory on human cells, after which they are tested on animals. However, none of these approaches can accurately reproduce the effect of drugs on human organs.

The authors managed to create miniature three-dimensional organs, or organoids, and combine them on a single platform that provides modeling of body functions and the ability to monitor the functions of the entire system with unprecedented accuracy to date.

The organoids created by the authors are made from cells that are part of human tissues using the method of three-dimensional printing and other cellular engineering technologies. The heart and liver were chosen to create the system due to the fact that toxicity to these organs is one of the main reasons for the failures of the development of experimental drugs and the withdrawal of medicines from sale. The lungs are a place of penetration of toxic substances and aerosol preparations, such as inhalation drugs for the treatment of asthma.

Organoids are placed inside a sealed monitored system equipped with a real-time camera. The viability of organoids is maintained with the help of a nutrient medium circulating in the system, into which potential drugs are also introduced.

First, the researchers tested the organoids for their similarity to human organs. For example, the micro-liver first received a high dose of a widely used analgesic drug, and subsequently another compound that neutralizes its toxic effects. The observed reaction to the toxic effect and the weakening of its manifestation after treatment exactly corresponded to the manifestations observed in patients.

However, the reaction to the drugs of the whole organism is much more important than the reactions of individual organs. Quite often, in the process of testing new experimental drugs, and sometimes even after the approval of the clinical use of new drugs, they have an unexpected toxic effect on tissues that are not a direct therapeutic target.

For example, if a drug is screened only on the liver, it is completely impossible to assess the potential side effect on other organs. Combining several organs into a single system can solve this problem, as well as save many lives and save huge sums.

The authors have worked out many scenarios in order to make sure that the "organism-on-a-chip" system developed by them reproduces multi-organ reactions to drugs. For example, they injected a drug used to treat cancer into the system. Obviously causing scarring of lung tissue, in the system it unexpectedly had an effect on the organoid of the heart. However, in the control experiment, the drug had no effect on the isolated heart model.

Based on this observation, it was suggested that under the action of this drug, inflammatory proteins leave the lung tissue and circulate throughout the circulatory system. As a result, the heart begins to contract faster, after which the contractions stop completely, which indicates the existence of a toxic side effect.

Currently, the authors are working on speeding up the system for larger-scale screening, as well as on introducing additional organs into it.

Article by Aleksander Skardal et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform is published in the journal Scientific Reports.