SARS-CoV-2 z-bo 2020-10-07 293

　　SARS-CoV-2 is a virus that can destroy lung, liver and kidney tissues grown in the laboratory and may explain the serious complications of COVID-19 in the human body.

　　Researchers are cultivating microorganisms in the laboratory to study how the new coronavirus damages the human body. Studies on these organoids have shown that there are multiple viruses in various invading organs from the lungs to the liver, kidneys and intestines. Researchers are also conducting drug trials on these small tissues to determine whether these therapies can be used to treat humans.

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　　learned from hospitalization and autopsy that SARS-CoV-2 may have devastating effects on organs. However, it is not clear whether this damage is directly caused by the virus or by secondary complications of the infection. Several research groups are using organoid studies to show where the virus spreads in the human body, infected cells and damaged cells. Thomas Effers, a cell biologist at Johannes Gutenberg University in Mainz, Germany, said: "The beauty of organoids is that they resemble the actual shape of tissue."

　　Animal cells cultured in petri dishes are used to study viruses. However, the researchers say that they cannot mimic what happens in the body and therefore cannot mimic SARS-CoV-2 infection very well. Núria Montserrat, a stem cell biologist at the Institute of Bioengineering of Catalonia, Barcelona, Spain, said that organisms can better demonstrate the effects of SARS-CoV-2 on human tissues. Montserrat said it can grow into cells containing multiple cell types and take on the form of primitive organs within a few weeks. It is also cheaper than animal models and avoids ethical issues.

　　However, Bart Haagmans, a virologist at the Erasmus Medical Center in Rotterdam, the Netherlands, said that the research on biological SARS-CoV-2 is very limited because they cannot reflect the interaction between human organs. effect. it is. Validated in models and clinical studies.

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　　An important finding of organic research is the effect of SARS-CoV-2 on respiratory cells from the upper respiratory tract to the lungs. Stem cell biologist Kazuichi Takayama and his colleagues have developed four types of bronchial animals made from frozen cells or epithelial cells of the bronchial layer in vitro. When his team infected SARS-CoV-2 with organoids, they discovered that the virus mainly targets stem cells. These stem cells can replenish epithelial cells called basal cells, but the virus cannot easily enter the protective secretion "club cells." The team published its findings about bioRxiv and is currently planning to study whether the virus can spread from basal cells to other cells.

　　The virus can enter the lungs through the upper respiratory tract and cause respiratory failure. This is a serious complication of COVID-19. Chen Shuibing, a stem cell biologist at Weill Cornell College of Medicine in New York City, used a miniature lung in a petri dish. The infection killed some cells and caused the virus to induce the production of proteins, such as chemokines and cytokines. I found it done. Great immune response. Many severe COVID-19 patients experience an immune response called a cytokine storm, which can be fatal.

　　However, Professor Chen, who also published the results of the bioRxiv study, said that the causes of lung cell death in patients are still a mystery, such as virus damage, self-destruction and swallowing by immune cells. Chen said: "We know that cells die, but we don't know how they die." He said that the method of making organoids is different from the alpine method. She did not use adult cells to make stem cells, but instead used pluripotent stem cells that could develop into any cell type in the human body. Organoids grown in this way may contain more cell types, but the end result is immature and may not be representative of adult tissues. Chen said he is currently using immune cells to grow lung organoids. SARS-CoV-2 can spread from the lungs to other organs, but until Montserrat and her colleagues published a research paper in the journal Cell on May 4, the researchers said the virus was not sure how to spread? In experiments using organoids also made of pluripotent stem cells, it was found that SARS-CoV-2 can infect endothelial cells (cells in the inner layer of blood vessels) and leak virus particles into the blood, thereby circulating throughout the body. Find. Joseph Penninger, a genetic engineer at the University of British Columbia in Vancouver, Canada, and co-lead author of the study, said that pathological reports of vascular injury in patients with COVID-19 also support this hypothesis. Penninger and Montserrat said that organoid studies have shown that when the virus enters the bloodstream, it directly infects multiple organs, including the kidneys. The virus infects kidney organoids and kills some cells, but researchers are not sure if this is the direct cause of kidney failure observed in some patients. Another study of liver organoids found that the virus can infect and kill cells that promote bile production, the bile duct cells. Zhao Bing, a cell biologist at Shanghai Hutan University, said that many researchers believe that liver damage in COVID-19 patients is caused by excessive immune responses or drug side effects. Zhao Bing's research results were published in the journal "Protein and Cell 6". His research "shows that the virus can directly attack liver tissue and cause liver damage."

　　Scientific research using intestinal organs shows that the virus is intestinal cells. It can also replicate in the cells of the small and large intestines. .. Hagmans, who developed intestinal organoids, said these findings are beneficial, but the use of organoids to study the interaction between viruses and their hosts is still in its infancy. "It is too early to say that they are related." Researchers have a better understanding of how viruses interact with the human immune system to cause damage. He said he needed a complex organic system.

　　Peninger said: "I firmly believe that the virus that causes COVID-19 can infect tissues other than the lungs and cause most diseases, but more serious consequences, such as kidney and heart damage, are caused by the virus. This may be infection and excessive The combination of immune response."

　　Scientists are still investigating whether organic-like substances can be used to simulate drug reactions in the body. doing. Researchers hope that organoids can be used to test potential COVID-19 therapies, some of which have entered clinical trials without extensive testing in cells and animal models.

　　Chen stated as follows. “Due to time sensitivity, many clinical trials are designed based on previous knowledge of other coronaviruses and started without careful evaluation of the model system. As a result, many trials have failed.”

　　Chen screened 1,200 drugs approved by the US FDA for the treatment of other diseases, and found that the anti-cancer drug imatinib can inhibit SARS-CoV-2 in lung tissue. Since then, some human clinical trials of the drug as a treatment for COVID-19 have begun. Other research groups have also tested the effectiveness of existing drugs against coronaviruses in organoids, with some success. Hagmans said: "At the end of this process, we can only see these systematic predictions about the efficacy of the tested drugs. This is a long-term process."