Nature: Study how SARS-CoV-2 destroys the human body and causes death with mini-organ!

, June 25, 2020 //BiovalleyBIOON /- SARS-CoV-2 the virus can damage lung, liver and kidney tissue grown in the laboratory, which may explain some serious complications in humans with COVID-19researchers are working on micro-organs in a laboratory to study how new coronaviruses can destroy the bodyStudies of these organs have revealed the diversity of the virus in invading organs, from the lungs to the liver, kidneys and intestinesThe researchers also conducted drug trials in these micro-tissues to determine whether these treatments could be used in humansdoctors learned from inpatients and autopsies that SARS-CoV-2 could have devastating effects on organsHowever, it is not clear whether the damage was caused directly by the virus or by secondary complications of the infectionSeveral research groups are using organ-like studies to show where the virus is spreading in the body, which cells it infects, and which cells it damages"The beauty of organ-like organs is that they are similar to the real form of tissue," said Thomas Efferth,ofCell Biology at the University ofin Mainz-Johannes Gutenberg, Germany,"
picture source: Bing Zhao
virologists often use cell lines or animal cells grown in a petri dish to study virusesBut the researchers say these do not mimic SARS-CoV-2 infections well because they do not simulate what happens in the body, the organism better at proving the role of SARS-CoV-2 in human tissue, said N?ria Montserrat, astem cellbiologist at the Catalan Institute for Biological Engineering in Barcelona, SpainThey can grow into cells that include multiple cell types and form the shape of the original organ within a few weeks, Montserrat saidThey are also cheaper than animal models and avoid the ethical implications of thembut Bart Haagmans, a virologist at Erasmus MC in Rotterdam, the Netherlands, said studies of SARS-CoV-2 in organ-like organs are limited because they do not reflect the interaction son-in-body organs, meaning the results still need to be validated in animal models and clinical studiesOne of the key findings ofinhalationorgan study is the role of SARS-CoV-2 in respiratory cells from the upper respiratory tract to the lungsKazuo Takayama, aof stemcell biology at Kyoto University in Japan, and his colleagues developed four different cell types of bronchial organs made from frozen or epithelial cells in the in vitro bronchial layerWhen his team infected the organ with SARS-CoV-2, they found that the virus was mainly targeted atstem cells,
which supplementing epithelial cells called base cells, but the virus did not enter protective secretion "club cells." The team published their findings on bioRxiv, and now they plan to study whether the virus can spread from the base cells to other cells virus can enter the lungs from the upper respiratory tract, causing respiratory failure, a serious complication of COVID-19 Watering Chen, a stem cell biologist at Weill Cornell Medical School in New York City, used microlungs in petri dishes and found that some cells die after infection, and that viruses induce the production of proteins such as chemofactors and cytokines, which trigger large-scale immune responses Many severe PATIENTS with COVID-19 have experienced an immune response called cytokine storms, which can be fatal But Professor Chen, who also published the study on bioRxiv, said it remains a mystery why a patient's lung cells died - whether it was caused by the virus, self-destruction, or because of immune cells "We know that cells will die, but we don't know how to die, " said Chen, who created organ-like methods differently from Takayama She uses pluripotent stem cells, which can develop into any cell type in the body, rather than using adult cells to make stem cells Organ-like organs that grow in this way can include more cell types, but the end result is immature and therefore may not represent adult tissue, Chen said, and she is now using immune cells to grow lung organs the of blood shock SARS-CoV-2 can spread from the lungs to other organs, but it wasn't until Montserrat and her colleagues published a study in the May 4 issue of the journal Cell that researchers determined exactly how the virus spread In an experiment of organ-like experiments, also made from pluripotent stem cells , they found that SARS-CoV-2 can infect endothelial cells -- cells in the lining of blood vessels -- allowing viral particles to leak into the blood stream and circulate throughout the body Josef Penninger, a genetic engineer at the University of British Columbia in Vancouver, Canada and co-lead author of the study, said the pathological report on vascular damage in patients with COVID-19 also supports this hypothesis Penninger and Montserrat say studies of organ-like studies have shown that once the virus enters the bloodstream, it directly infects several organs, including the kidneys Although the virus infected the kidney organs and some cells died, the researchers were not sure if this was a direct cause of the observed renal insufficiency in some patients another study of liver organs has found that the virus can infect and kill cells that promote bile-generating cells, or bile duct cells Bing Zhao, a cell biology at Fudan University in Shanghai, said many researchers believe that liver damage in patients with COVID-19 is caused by an overactive immune response or side effects of drugs Bing Zhao's findings are published in the journal Protein and Cell6 His research "shows that the virus can attack liver tissue directly, leading to liver damage." "
according to a scientific study using intestinal organs, the virus can also replicate in cells arranged in the small intestine and the large intestine, or intestinal cells Haagmans, who developed intestinal organs , said that while the findings are instructive, the use of organ-like organs to study viral-host interactions is still in its infancy "It's too early to say how relevant they are." Researchers say more complex organ-like systems are needed to better understand how viruses interact with the body's immune system to cause damage Photo Source: Joep Beumer Clevers Group Hubrecht Institute Penninger: "We are now quite convinced that the virus that causes COVID-19 can infect tissues outside the lungs and, to a large extent, cause disease." But more serious consequences, such as kidney and heart damage, may be due to a combination of viral infections and over-immune responses "
drug testing beds
scientists are also studying whether organs can be used to simulate the drug's response in the body The researchers hope that organ-like organs could be used to test potential COVID-19 therapies, some of which have rushed into clinical trials rather than extensive testing on cellular and animal models "Due to time sensitivity, many clinical trials based on previous knowledge of other coronaviruses and started without a careful evaluation of the model system," chen said As a result, many people have failed , Chen screened 1,200 drugs approved by the FDA
fda for other diseases and found that the anti-cancer drug imatinib inhibits SARS-CoV-2 in lung tissue Since then, several human clinical trials of the drug as a COVID-19 therapeutic drug have been launched
other research teams are also testing the effectiveness of existing drugs against coronaviruses in organ-like organs, with some success "We only know at the end of the process the predictive value of these systems for testing drug efficacy," Haagmans said This is a long-term process " (BioValleyBioon.com) References: 1
Mini-Organs the shoman's body
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4: In Vitro and Animal Models for SARS-CoV-2 research
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India pushes for the animals in biomedical research 6
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SARS-CoV-2ly infects human gut gut into sifocytes .