How does "Homunculus" work?
Homunculus will grow a heart
Scientists have invented a bioreactor in which human organs are cultivatedLarisa Aksenova, <url>
The development of Russian scientists is a step towards the introduction of test systems that allow to study the effect of drugs on several cell cultures at once, in conditions close to the human body.
The "big race" to create multi-organ dynamic systems in vitro began in 2012, when a large-scale project was launched in the USA, for which $ 200 million was allocated. A new institute was created, dozens of the largest laboratories were involved and the deadline was rigidly fixed – five years. Europe also plans to allocate significant funds for the development of such systems under the Horizon 2020 Research and Innovation program with a total budget of 80 billion euros, which will replace the Seventh EU Framework Program in 2014. Such developments are being intensively carried out in Russia, in the scientific and technical center "Bioclinicum".
Today, many laboratories in the world can not only maintain human cells in culture for a long time, but also direct their growth and development in the right direction – to form the similarity of tissues and organs. Modern advances in biomedicine allow us to go further in the creation of artificial systems.
If it is possible to grow separate organs, then why not cultivate them together? Since this activity is very expensive and intelligence-intensive, first you need to convincingly justify: for what purposes such a system may be needed.
It turns out that such in vitro systems are very much in demand. There is a lot of talk that experiments on laboratory animals are unethical. But even if this argument is not taken into account, it often turns out that a new drug that has proven itself remarkably well in preclinical trials on guinea pigs or experimental mice leads to dramatic results in clinical trials.
Here is just one fact that shocked not only the residents of London, but also the entire world community in 2006. Six absolutely healthy young people who participated in clinical trials of a new drug for autoimmune diseases and leukemia (the drug anti CD28 TGN1412) were in intensive care with allergy symptoms unknown to doctors, more pronounced than with Quincke's edema, and then received the collective name "elephant man". Perhaps this would not have happened if there had been a test system, a micromodel of the human body, as close as possible to real conditions.
A model that takes into account not only the effect of drugs on specific organs, but also the methods of administration into the body (their metabolism strongly depends on this) – in the form of a tablet through the gastrointestinal tract or intravenously, intramuscularly (this is a physical model of the action of drugs, unlike the mathematical models already used, which I wrote aboutГазета.ги".)
Cosmetic companies such as L'Oreal and Uniliver refuse to use animals to test their new products primarily because commercial test systems with human skin cell culture are a more adequate model for assessing the effects of chemicals. At the same time, some components of creams and ointments are able to penetrate through the skin and spread through the circulatory system throughout the body. Our main recycling organ is the liver, it protects the body from unwanted effects. This means that the following situation should be modeled in the test system: the substance is applied to the skin, it penetrates inside, is picked up by the culture medium washing the cells, the composition of which is as close as possible to the blood serum, and is delivered to the liver cells, where it is neutralized. If we take samples of the culture medium, then ideally we will find this substance "at the entrance", and it should not be "at the exit".
Test systems are also needed to select the optimal treatment regimen for patients with drugs already known and used in medicine. For example, in order to choose the most effective medicine for the treatment of a specific infection, doctors make bacterial cultures for sensitivity to various antibiotics. This is a routine procedure. And you can take a small number of cells of a diseased organ and, under the same conditions, test these cells for sensitivity to drugs. If we manage to develop a technology for such testing, it will be a very important step in the development of personalized medicine, which is being talked about so much now.
"Homunculus"The Scientific and Technical Center "Bioclinicum" was established in 2008.
Scientists of various specialties work here, because to create such a test system requires the qualification of specialists from different fields of science - biology, electronics, pneumatics, hydrodynamics. We need mathematicians who are able to make calculations, and engineers who are able to translate ideas into design solutions. "The creation of a test system, which we called the microbioreactor "Homunculus", began to be thought about relatively recently. At the end of 2010, our supervisor, corresponding member of the Russian Academy of Sciences Alexander Grigoryevich Tonevitsky discussed this idea with a former graduate student, now a doctor of sciences, professor, head of the laboratory at the Technical University of Berlin Uwe Marx, - tells the correspondent of "Gazeta.En" the general director of "Bioclinicum" candidate of biological sciences Dmitry Sakharov. – Since 2010, we have started developing this idea in parallel with our German colleagues on the basis of cooperation. We have attracted partners from other scientific institutions, in particular from the Franugofer Institute in Dresden, in order to better understand how models function, how this or that body functions. The whole year 2010 was spent in discussions and discussions: how to approach the solution of the problem. Uwe Marx started developing models of organs, and in 2011 we connected with the engineering part."
What is the modern version of the homunculus – "man on a chip"?
The installation consists of two parts – the chip itself, in six cells of which cells of organ models (intestines, liver, lungs, heart, brain, skin) are cultured, and a control unit with which all parameters of the culture medium washing them are set. In a closed system, conditions have been created that simulate the "life" of one hundred thousandth of a person – both in terms of the number of cells and the amount of liquid washing them.
The fluid velocity is calculated in such a way as to correspond to the velocity in the finite capillaries of a real human body. Since our main motor – the heart – creates pulsation, as a result of which all the cells of the body experience mechanical deformation (stretching-compression), imitation of this process in the "Homunculus" is achieved through the operation of the valves of pumps pumping fluid into the installation. Both the rate of fluid renewal and the sequence of its receipt to the models of organs on the chip are taken into account: for example, the "intestine" is directly connected to the "liver" (the portal vein of the liver is simulated). In addition, fresh culture fluid is supplied to the liver (the hepatic artery is imitated).
The chip also provides compartments for installing biosensors – electrochemical and optical sensors for analyzing the homeostasis of the environment in order to maintain concentrations of nutrients and metabolites within physiological limits. There is a zone where the enrichment of the medium with 2 is carried out: through two closely spaced capillaries, under the influence of diffusion through the polymer layer, carbon dioxide enters the culture medium. This allows you to do without a CO2 incubator and maintain the acidity of the medium (pH). The thermostating system helps to maintain a constant temperature of 37 ° C or any other if it is necessary to simulate heat stress.
"We are not saying that we are completely emulating the body, but we have definitely stepped forward and are moving from a mixture of static cell cultures to a certain model of human organs," explains Dmitry Sakharov.
– So far we are working with cancer cell lines, not with primary ones. Why? To create standard conditions. There are commercial cell strains on the scientific market. And our task is to select the cancer strains closest to the main human organs so that the results can be reproduced in other laboratories."
Before placing cells in a bioreactor, they are cultured in tablets for several weeks, differentiation is induced – specialization, the success of which is judged not only by external signs (for example, intestinal epithelial cells form microvilli), but also by biochemical markers (hepatocytes begin to synthesize albumins and cytochromes). In addition, cells growing on a porous polyethylene membrane make themselves an additional "substrate" – a matrix of collagen, and self-organize into a spheroid structure. The substances under study can be injected directly into the cell (simulating percutaneous or oral administration) or into the culture medium (simulating intravenous administration) and monitored by measuring biochemical and growth parameters, which metabolites are released, and how they affect the work of other "organs" in the system.
Microbioreactors "Homunculus" are already in the laboratory of Uwe Marx in Berlin and in the Novosibirsk Scientific Center for Clinical and Experimental Medicine of the SB RAMS, where they work out the technique of tissue cultivation. At the same time, there are still many different tasks to be solved, not only of a technical, but also of a moral and moral nature. For example, which sources of human tissue to use. What is the maximum possible degree of emulation of the human body in such systems. How to regulate the legal aspects of the use of cell cultures provided by patients. Whether it is necessary to create biobanks of cell cultures and, if necessary, how to legislatively regulate this issue. And, finally, whether society is ready to accept test systems in the form of a human model.
Portal "Eternal youth" http://vechnayamolodost.ru22.04.2013