06 March 2020

Superman-on-a-chip

Researchers from the Wake Forest Institute for Regenerative Medicine (WFIRM) have created a system of organoids that can be used to detect harmful and side effects of drugs before being introduced into clinical practice. The use of such a system for screening potential pharmaceuticals can significantly accelerate the entry of new drugs into the market and reduce the cost of clinical trials, as well as reduce the volume of animal trials.

The system is built from many types of human cells, which are combined into tissues representing most organs of the human body, such as the heart, liver and lungs. Each of these miniature organs is a small three-dimensional tissue-like structures about the size of one millionth of an adult organ.

An important feature of this system of human body tissues is the ability to determine the toxicity of a drug to a person at a very early stage of development and its potential for personalized treatment. Abandoning further development of problematic drugs at an early stage can save billions of dollars and indirectly save a large number of human lives.

The group has already worked on chips with models of individual organs and their groups, which determined the toxicity of many drugs approved for the treatment of humans, and subsequently withdrawn from the market due to the high risk of serious adverse effects. The toxicity of the recalled drugs was not immediately detected in studies using standard two-dimensional systems for cell culture and animal models, adverse effects were also not detected at all three levels of human clinical trials. And the systems developed by a group from WFIRM could easily detect toxicity.

In the new study, due to certain individual requirements for each type of tissue, a set of tools of biotechnological methods was used to create mini-organs. Small samples of human tissue cells were isolated and turned into miniature versions of a human organ. They can contain blood vessel cells, immune system cells, and even fibroblasts – connective tissue cells. Each of these mini-organs performs the same functions as the organs of the human body, for example, the heart beats about 60 times a minute, the lungs absorb air from the environment, and the liver breaks down toxic compounds into harmless waste.

This approach is justified: in order to simulate various reactions of the body to toxic compounds, a system is needed that includes all types of cells that produce these responses.

Another distinctive feature of the new imitation of the human body is blood circulation. Each model of an organ on a chip contains a medium – a liquid with nutrients and oxygen, which circulates between all types of organs, carrying out gas exchange and removing waste. For these purposes, microfluidics is usually used, according to the basics of which the tested medicinal compounds are recycled and decay products are removed.

A group of researchers realized that drugs and toxic molecules do not move strictly from one organ to another. Instead of transferring the studied drug from one organoid to another, the researchers created a microfluidic circuit that repeatedly conducts the drug through each mini-organ in the same way as the heart recycles molecules with blood through the human body.

The system of mini-organs is the result of long and large–scale work. The creation of microscopic human organs for drug testing was a continuation of the extensive work on the creation of human-scale organs, which has not stopped for almost three decades. During this time, more than 15 technologies for creating tissues and organs, including muscles, bladder and vagina, have been tested on humans in clinical studies.

Article by A.Skardal et al. Drug compound screening in single and integrated multi-organoid body-on-a-chip systems is published in the journal Biofabrication.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Wake Forest scientists create the world's most sophisticated lab model of the human body.


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