Nature has recently published a news article talking about how mini lungs and other organoids helping to beat COVID. The article describes how researchers have built mini lungs, guts, livers, brains, and more to study how SARS-CoV-2 infects organs.

Organoid technology and its potential usage

Organoid technology had previously been utilized mainly to examine basic human biology, development and related disorders, and cancers, with only a few labs employing the models to study viruses and other infectious diseases. Hans Clevers, a developmental biologist at the Hubrecht Institute in Utrecht, commented that the pandemic has brought organoids to center stage, driving high-impact papers and establishing their value for drug development in the article.

The new article also described that in exploring the organoid technology’s full potential, scientists still need to find ways of growing more complex systems, like adding immune cells and blood vessels. Jie Zhou, a virologist at the University of Hong Kong, commented that ‘the use of organoids to study viruses is only at its infancy in the article.

SARS-CoV-2 can infect a host of mini organs

A paper published in 2020 in Science showing that SARS-CoV-2 was readily replicated in mini guts. The new article on nature outlined that this study helped to explain why some people with COVID-19 have had digestive problems, including diarrhea and vomiting, and have identified another possible route of transmission. It also stated that researchers have shown that SARS-CoV-2 can infect a host of mini-organs, from the liver to kidneys to the brain – mimicking the multi-organ damage seen in some people with COVID-19.

Discovery of the role of club cells in the lung on SARS-CoV-2 replication using organoid technology

For people with severe COVID-10, the site of pneumonia is buried deep in the lungs called alveoli. These cells are hard to access and study. The news article describes how viral immunologists using organoids made from alveoli to investigate infection. It outlined that the researchers found the virus ran riot in organoids made from alveoli and from cells in the tiny airways that feed them. It stated that, in the alveoli, SARS-CoV-2 targeted the cells that cover the air-exposed surface, which is rich in the ACE2 receptor through which SARS-CoV-22 gain entry. It also described that the virus can affect cells in the airways that secrete a molecule for dealing with the constant stretching in the lungs, called club cells.

‘Without organoids, I don’t know that we would have discovered that club cells could support SARS-CoV-2 replication because nobody would have thought to put it on club cells,’ says Catherine Blish, a viral immunologist at Stanford University in California.

Using gut organoids and gene-editing technique CRISPR to study viral entry

Scientists were also eager to learn more about how the virus gets into cells. The news article quoted a study of researchers to use gene-editing technique CRISPR in gut organoids in identifying two proteins – TMPRSS2 and TMPRSS4, together with ACE2, which can facilitate the virus’s entry. It also outlined that other labs are knocking out ACE2 entirely, to see whether the virus can still get in. ‘The more we study organoids, the more we realize that different types of cells use different mechanisms to support viral entry,’ says Hubing Chen, the stem-cell biologist at Weill Cornell Medicine in New York City.

Organoids help to fill the gap between watching the virus in cell lines and animal models

An unobstructed view of the virus rattling through the body could help researchers to find ways to stop it. Arinjay Banerjee, a coronavirus researcher at the University of Saskatchewan in Canada, commented in the news article that, ‘organoids help to fill the gap between watching the virus in cell lines, which lack the complexity of real tissue, and in animal models, which mirror human infection poorly and are expensive.’ 

Potential of organoids for drug discovery

Many research groups are exploring the potential of organoids for drug discovery. In the news article, Hubing Chen, the stem-cell biologist at Weill Cornell Medicine, commented that she has tested around 1000 drugs on mini colons and mini lungs, and has identified seven that look promising, including the antiviral drug remdesirvir, that had already been shown to have some benefit for participants in clinical trials. Chen also commented in the news article that her results as proving the utility of organoid screening. She described that the 15,000-drug-screen in lung organoids was her largest attempt yet in the article.

Organoids have been used to test vaccines

The new article outlined research findings on COVID-19 vaccine testing using tonsil organoids. It described that when researchers added a COVID-19 vaccine candidate, some of the tonsil organoids produced an immune reaction, generating killer T cells, as well as antibodies that could target the spike protein on the surface of the virus. However, it commented that much research is needed to be performed to figure out whether what transpires in a dish reflects what will happen in the body. In addition, as organs in the body don’t exist in isolation, in learning what happens when a person is infected with SARS-CoV-2 and whether therapies will work, the article describes that researchers will need a more complex system that includes immune cells and blood-vessels cell.

In the ideal world, researchers want to be able to connect organoids. ‘The dream for every virologist would be to have different organs connected.’ Says Elke Muhlberger, a virologist at Boston University in Massachusetts in the news article. ‘The closer we can get to the human organ, the better it will be, the more we will learn about why viruses are so pathogenic.’

The full article of nature news article is available here: www.nature.com/articles/d41586-021-01395-z.

Reference:

Mallapaty, Smriti. The Mini Lungs and Other Organoids Helping to Beat COVID. Nature, 26 May 2021, www.nature.com/articles/d41586-021-01395-z.

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