Nature (UK): miniature organs show how the coronavirus affects the body

Scientists grow in the laboratory miniature organs, to understand how the new coronavirus affects the human body. Studies of these organelles show that the virus will infect a variety of organs, including the lungs, liver, kidneys and bowels. The researchers also are experimenting with different drugs in these mini-tissues in an attempt to understand whether such drugs to treat people.

Studying hospitalized patients and autopsy results, doctors realized that SARS-CoV-2 can have a devastating impact on human organs. But it’s unclear whether these lesions directly by the coronavirus, or secondary complications due to infection. Exploring the organelles, numerous groups trying to figure out where in the body the virus moves to the cells it infects and the damage being done.

“The beauty of organelles is that they resemble the true morphology of the tissue,” says cell biologist Thomas Effert (Thomas Efferth) from the Johannes Gutenberg University, in Mainz, German.

Usually virologists investigate viruses using cell lines or cultured in the laboratory cages of the animals. But it is impossible to efficiently simulate the infection of SARS-CoV-2, because these cells do not mimic what is happening in the body.

The organelles better show that SARS-CoV-2 does to the human tissue, says an expert in the field of biology of stem cells núria Montserrat (Núria Montserrat), working in Barcelona in the Catalan Institute of bioengineering. You can grow a variety of cell types, creating the form of the original body in a matter of weeks, she said. In addition, it is cheaper than using animals, and thus there is no ethical challenges.

However, studies of SARS-CoV-2 on the organelles have their drawbacks, as in this case, it is impossible to consider the interaction between bodies. This means that the results need to test on animals and in clinical trials, says virologist Bart Haagmans (Bart Haagmans), working at the medical center of the Erasmus University Rotterdam.

One of the key objectives of the research the organelles is to clarify that the virus SARS-CoV-2 makes cells in the respiratory system, starting with the upper respiratory tract and to light.

Specialist in the field of stem cell biology from Kyoto University Kazuo Takayama (Takayama Kazuo) with their colleagues have created bronchial organelles of the four types, taking the frozen cells of the outer shell of the bronchial epithelium. When the scientists infected the organelles SARS-CoV-2, they found out that the virus mainly affects the stem cells that reproduce the cells of the lower layer of the epithelium, however, hardly penetrates the protective secretory cells. Scientists have made their work on the bioRxiv website, and now want to find the answer to the question of whether the virus spread from the cells of the lower layer of the epithelium on other cells.

From the upper respiratory tract, the virus can enter the lungs and cause respiratory failure, which is a severe complication COVID-19. Using mini-light out of the tube, an expert in the field of stem cell biology Huibin Chen (Shuibing Chen) from the Medical College Weill Cornell showed that some infected cells die, and the virus contributes to the production of proteins of chemokines and cytokines, inducing a powerful immune response. Many people with severe COVID-19 face an immune response called cytokine storm, which is deadly.

However, Chen also posted their results on bioRxiv, says that it is unclear why lung cells in humans die. Maybe it is the result of exposure to the virus, maybe it is self-destructive, and can kill the immune cells. “We know that cells die, but do not know how,” she says. Her approach to the creation of organelles differs from the method of Takayama. Instead of having to create them from adult cells, Chen used pluripotent stem cells, from which the body can create cells of any type. Grown in this way, the organelles may include more cell types, but the target tissue is less Mature and is adult tissue, says Chen, who currently grows the organelles of the lungs in immune cells.

From the lungs of SARS-CoV-2 can penetrate other organs. However, scientists were unsure exactly how the virus moves, while Montserrat with colleagues published on 4 may, the results of their research. During the experiments, with organelles, also grown from pluripotent stem cells, they found that SARS-CoV-2 can infect the endothelium (layer of cells lining the inner surface of blood vessels), allowing viral particles enter the blood and spread throughout the body. This hypothesis is confirmed by the results of the autopsy from COVID-19 and study of damaged blood vessels, says a genetic engineer Joseph Penninger (Josef Penninger), working in Vancouver at the University of British Columbia and became a leading co-author of the study.

Studies on organelles indicate that once in the blood, the virus can directly infect several organs, including the kidneys. Although the virus has infected the organelles of the kidneys and some cells died, scientists do not know exactly whether it is the direct cause of renal function, was observed in some patients.

In another study on liver organelles found out that the virus is able to infect and kill cells cholangiocyte promoting the secretion of bile. Many scientists believed that liver damage was observed in cases COVID-19 caused by excessive immune response or side effects from drugs, says cell biologist Bin Zhao (Zhao Bing), working in Shanghai in Podansko University. In their study, the results of which are published in the journal “Protein and cell”, he concludes that the virus can directly attack the liver tissue, and it causes her defeat.

The virus can also be reproduce in the cells enterocytes that make up the epithelium of the small intestine and colon, as evidenced by these studies on the organelles of the intestines, published in the journal “Science”.

These studies are very informative, however, the use of organelles to study the interaction of the virus-host is still in its infancy, says Haagmans who raised the organelles of the intestine. “It is too early to say how they are relevant”, — said the scientist. We need a more complex system of organelles to better understand how the virus interacts with the immune system, causing lesions of the body.

“Now we already have pretty solid confidence that the caller COVID-19 virus can infect tissues outside the lungs and greatly aggravate the disease,” says Penninger. However, more severe outcomes of the disease, associated with damage to the kidneys and the heart, probably caused by a combination of viral infections and excessive immune response, he explains.

Scientists also want to understand whether you can use organelles to simulate the effects of drugs on the human body. They hope that the organelles can be used to test potential drugs from COVID-19. Somewhere in the hastily clinical trials are conducted without a large-scale checks on cells and animals.

“Because of the time factor many clinical tests were prepared on the basis of existing knowledge about other coronaviruses, and carried out without a careful assessment models, says Chen. In the end, many of them failed”.

Chen investigated approximately 1 200 drugs approved by FDA food and medicines for the treatment of other diseases, and found that the anticancer drug imatinib inhibits the virus SARS-CoV-2 in organelles of the lungs. Then began several clinical trials of this drug on people as a treatment for COVID-19.

Other teams also have existing cures for coronavirus in the organelles, achieving some success. “We are only at the end of the process find out what is the predictive value of these systems for testing effectiveness of medicines, says Haagmans. Is a long process.”