"Body-on-a-chip"
Technology prospects
Ivan Sychev, Geektimes
Every new drug to enter the market takes several years and billions of dollars, of which more than half is spent on research. Animal testing does not provide a definitive answer about the effectiveness of drugs: drugs that have worked on mice may be useless to humans. Medications that work for the bulk of people may not be suitable for one particular patient, which leads to the need for personalization.
One of the ways to solve these problems was the "organ-on-a-chip" concept. A group of scientists working with DARPA went further: she is working on creating an "organism-on-a-chip" to find drugs that are fully compatible with the patient and to study their side effects.
A group of scientists within the framework of the project has created a microfluidic platform to simulate the interaction of up to ten human organs. The system is designed for drug testing.
"With our chip, you can inject a drug and test its effect on several organs, measure the metabolism of the drug," says Linda Griffith, head of the research team. Scientists note that one of the main applications of the system will be the verification of immunotherapeutic drugs: the results of their testing on animals are very difficult to translate into humans.
When developing new drugs, researchers determine its purpose – they answer the question of what the drug should affect, based on knowledge about the disease itself. Then they create compounds that have the necessary effect on the organ. Preclinical animal trials should show the safety and efficacy of the drug before testing in humans, but cannot identify potential side effects. In addition, Griffith argues, the drugs may later fail in human trials. In some cases, it is impossible to test the drug on mice or rats – for example, these animals are not infected with enteroviruses that are deadly to infants.
The technology that Griffith and her colleagues are developing for DARPA, scientists have called "physiome-on-a-chip." The researchers needed a platform that allows tissues to grow, interact with each other, mimicking the functions of human organs.
"Organ-on-a-chip" is a multi-channel microfluidic system that allows you to simulate the interaction of drugs with the heart, lungs, intestines and other organs. For example, the heart tissues on the chip after they were loaded onto the device began to pulsate with the frequency of the normal pulse of an average adult – from 55 to 80 beats per minute, and after half an hour of exposure to a drug for the treatment of bradycardia, the "pulse" increased to 124 beats.
Pulsation of heart tissues
The "thrombosis-on-a-chip" model allows you to simulate the factors leading to the formation of blood clots. "Brain-on-a-chip" has learned to grow blood vessels on its own. In theory, the "packaging" of living cells into a microcircuit can make it possible to abandon animal experiments and increase the effectiveness of drug testing.
An important factor in favor of working with "organs-on-a-chip" is the possibility of personalization of drugs. Side effects and effectiveness of the drug may depend on the genetics, age, lifestyle and other indicators of a particular patient. A miniature "organ" of a particular person will allow you to understand how the drug will affect him.
The new development develops this direction and makes it possible to understand not only the effect of the drug on one organ, but its effect on a system of several organs, a "man in miniature". The second difference from the "classic" "organs-on-a-chip" was the openness of the system: tissues can be removed for their analysis without interrupting the operation of the device. The pump system allows you to regulate the distribution of fluids between organs, simulate the circulation of blood, immune cells and proteins in the human body. Additional tissues can be introduced into the system, such as a tumor inside the organ.
The result was several versions of the chip, including tissues of up to ten types of organs: liver, lungs, intestines, endometrium, brain, heart, pancreas, kidneys, skin, muscles. Each "organ" consists of a cluster of 1-2 million cells. Tissues are not a copy of an organ, but are capable of performing some of its important functions. It is possible to use cells of a specific person in the system – it is more difficult to work with them, but this approach is more effective for searching for personalized drugs.
The device allows researchers to see how a drug that enters the body through the mouth is transported to other tissues and metabolized. They can check how the drug moves between organs, affects various tissues and disintegrates.
"Microphysiological systems simulating one organ can be successfully used for testing in the pharmaceutical industry and for organ research. But the huge potential of this concept is associated with the unification of several organs on one chip for in vitro pharmacology. This study illustrates how an approach to a multi-microphysiological system combining the genetic background of human cells allows us to accurately predict the pharmacokinetics of drugs, their distribution, metabolism and excretion from the body," Kevin Healy, a professor of bioengineering at the University of California at Berkeley, who is not associated with the group of researchers, comments on the results of the work.
"Physioma-on-a-chip"
Linda Griffith's lab is currently working on a chip to search for drugs for Parkinson's disease: the system includes the brain, liver and tissues of the gastrointestinal tract. With the help of this "organism-on-a-chip", the team will test hypotheses that bacteria found in the intestine can influence the development of this disease.
Another application is associated with modeling tumors that metastasize in other parts of the body. Among the advantages of the system, Griffith calls the ability to scale it and use various configurations. For commercialization, the most promising solution at the moment will be the creation of systems from three to four organs, since this "minimum" will allow obtaining more valuable information compared to systems from one organ.
Portal "Eternal youth" http://vechnayamolodost.ru