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The man on the Chip

made As the message is the round, raised you with big dreams. For the first time, a human Organ in miniature was grown in a lab. What would be possible! Physicians could, in the future, observe the Interaction of different cells in the laboratory and, finally, the development and function of organs in Detail. Scientists have bred well mini livers and pancreatic glands, tiny bladder, and Plazentas. Recently succeeded for the first time, to win human blood vessels as mini organs in the lab.

Meanwhile, doctors and biologists to combine different mini-structures in the laboratory, to understand their interaction. Together with the engineers put their new varieties, even at the micro-chips. So you want to simulate the natural environment of the organs in the body. If it goes according to some scientists, can you link soon, all of the major organ systems and the whole human on a chip to study, to research diseases and test drugs.

"These new technologies have the potential to revolutionize drug development," says Peter Loskill, and Bioengineering at the Fraunhofer Institute for interfacial engineering and biotechnology IGB in Stuttgart and the University of Tübingen. And it is less animal testing would be needed, to which it has given in recent times in Switzerland, many of the discussions.

Unforeseen side effects

so Far, the development cost for an approved new drug for up to 2.8 billion euros. "These immense costs, would reduce the industry, of course," says Marlon Schneider from the Federal Institute for risk assessment (BFR) in Berlin. Still, researchers rely on animal tests to check whether substances act. It is only when you are in the animal experiments as safe, it is allowed to test on humans. But the test series, the pet often reveal little about the processes in the human body. Of the ten substances, which act in the animals, by dropping nine in Tests on humans. Sometimes, with terrible consequences for the subjects.

According to the legally prescribed animal experiments, the active substances in the Phase 1 of the clinical drug testing, the first Tests on humans. In healthy subjects, a physician will then check what is the active ingredient in the body triggers and, especially, how well people tolerate. Here it comes sometimes to unforeseen side effects, for example, more than ten years ago with the antibody TGN1412.

In rats and mice had disorders to the new substance auto-immune diseases such as rheumatoid Arthritis and multiple sclerosis can fight. Side effects were not encountered. Even in Tests on monkeys with the 500-fold of the planned dose, no abnormal reactions were noticed. In the first clinical Tests in humans in a British hospital, the subjects wound up, however, after just a few minutes before the pain shortly after the injection of the antibody. Their heads and neck swelled spooky, some suffered failure, multi-organ. "It is extremely important that results of animal experiments can be better transmitted to humans," says Schneider.

Organoids in the lab should respond to drugs in the same way as the real Organ.

Therefore, the researchers want to test new substances in the future, mini-institutions. For this, they embed human stem cells in a Gel. The Organoids grow, so small that they are visible with the naked eye as black dots. Under the microscope, shows, that most of the organs contain the essential structures of the real organ. Therefore, the Organoids in the lab on drugs should respond in the same way as the real Organ in the body. For people with cystic fibrosis, a rare genetic disease, was able to show the Dutch physician Hans Clevers. Together with colleagues at the Hubrecht Institute in Utrecht, he grew stem cells from the rectum of the patient and examined the resulting mini-organs new drugs. "What showed in the Organoid effect, actually helped the patient," says Clevers. In a Europe-wide study aim to investigate the to the mini casings of 500 cystic fibrosis patients and, therefore, one of the most urgent questions with a definitive answer: whether the mini-organs, in fact, the interior of the real organs.

interaction of the organs

you Should distinguish themselves, might be to try the Organoids in the future, a kind of precursor to the legally prescribed animal: "Only those active ingredients that have proven themselves in the Organoid, would you examine in animal experiments", says the veterinary Marlon Schneider. That alone would reduce the experiments on mice and rats, it drastically.

Many researchers want to achieve more. You want to know more about how a substance on various organs and on their Interaction with each other. Therefore, scientists today, begin to connect the tiny Structures in the laboratory. The Biotechnologist Reiner Wimmer from the Institute of Molecular biotechnology in Vienna, had reported in January in the journal "Nature" about the first mini blood vessels from the laboratory. Now he wants to combine this with other organo-chlorides. "Blood vessels are important for the maintenance of our bodies is essential, since they supply our cells with oxygen and nutrients and immune cells to transport", says Wimmer.

he would like to be guided as close as possible to the human development. The brain, for example, is formed vessels in the embryonic development, initially without blood. Later, the brain tissue sends out chemical messengers to the blood vessels attract. The Hiking then from the outside into the brain tissue. This process would re-enact Wimmer in the culture dish, he combines the brains of his miniature blood vessels with Mini. "We expect that dieGehirnorganoide produce similar signals, such as in human development."

lung model simulates breathing

The Biotechnologist would like to go a step further. He will be a mini blood vessel in a Biochip to it via mini pumps fluid to flow through. So he can find out under very controlled conditions, for example, where and when the immune cells attach in an inflammatory reaction at the vessel wall. In the future, as Wimmer is sure to be Organoids and Organ-on-a-chip fuse technologies.

But first, if you relate the influences of adjacent tissue, can scientists of different scenarios in the body to exactly mimic. "If we know the processes in the body accurately, then we can bring you targeted out of balance, disease research and drug testing," said Loskill. At the Wyss Institute in Boston, about researchers have already developed a lung model that simulated the bubble only breathing in the lungs. Even a pulmonary edema could trigger it in such a micro-chip and successfully treat.

organ systems combine

The company Tiss-Use in Berlin already has 16 single organ models are developed directly with cells from the human body, groups of cells, which is less complex than the classic Organoid. Chips with a maximum of four fabric combinations are already managed. Each Time, the scientists will need two to three months to find a medium that gets all of the tissues of the combination. "Similar to the skin's other needs in the body, the liver, the same is true on the micro chip," says managing Director Uwe Marx.

Soon, to Marx, to combine the ten organ systems to each other. This Human-on-a-chip, human-on-Chip, would be powered by an artificial circulation. So far, bio-engineers can simulate your in the small channels of the microchip and the flow of blood to the real organs. "Give us a year," says Marx. Before long he is working with the pharmaceutical industry to create, at their request, new links. The companies put the Biochips for internal experimentation, for the approval of medicines, it needs yet still experiments on animals.

by 2030, you could try 70 percent of the animal due to multi-organ chips to replace, believes Marx. Other colleagues such as Marlon Schneider from the BFR are skeptical. In the year 2017, 50 percent of the animal took place alone, experiments in basic research. Biochips are intended predominantly for testing the effectiveness or potential risks of drugs. "For the basis of research, they are far less suitable," says Schneider. In the long term, the veterinarian sees a huge potential for the chip technology, but they were not yet so far. "You can't animal to replace attempts at any price," he says. Finally, the safety of the patients.

(editing Tamedia)

Created: 12.03.2019, 20:51 PM

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