Integrating immune cells to organoids opens doors for viral research

How does a virus enter an organ? And how does the virus replicate inside the cell? Scientists can find answers to questions like these with organoids: three-dimensional mini organs, grown in the laboratory from human tissue.

So far, it has been difficult to use organoids to study the immune system’s response to a viral infection, because most mini organs do not contain immune cells. That has now changed at the Department of Gastroenterology and Hepatology of the Erasmus MC.

Macrophages

‘It was time to leverage our epithelial organoids’, says PhD student Kuan Liu. After almost a year of experimenting with culture conditions, he and his team succeeded in adding macrophages to liver organoids and to intestinal organoids. They chose macrophages because those immune cells play a crucial role in inflammation.

This video shows green-colored macrophages integrating into liver derived organoids.

The addition of immune cells to organoids opens new doors for virology research. It makes it possible to study the immune system’s response to a viral infection. This is important because it is usually not only the infection itself but often the subsequent excessive inflammatory response that is pathogenic. The macrophage integrated organoids make it easier to study that inflammatory response and disease manifestations more closely.

It is usually not only the infection itself but the excessive inflammatory response that is pathogenic

The new immune enhanced organoids can be used to study many viruses. For example, the hepatitis E virus which infects the liver and causes hyperinflammation and tissue damage, triggered by immune cells. As another example, rotavirus infects the intestine and is the leading cause of diarrhea. Other viruses, like SARS-CoV-2 and mpox virus can also manifest in the liver and intestine. The researchers saw that infection with these viruses leads to a storm of inflammatory substances in the macrophage-integrated organoids.

Test new treatment strategies

The scientists are also using the immune cell enriched organoids to test potential new treatment strategies that simultaneously target the virus, inflammation as well as tissue damage. This successful further development of organoids comes at a good time, because the American FDA recently announced its intention to reduce the use of laboratory animals for drug research. ‘Organoids can be a good starting point on the route to replacing laboratory animals’, one of the research leaders Pengfei Li explains.

The organoids with macrophages are not yet mature as far as the team is concerned. The mini organs now have been tested for about 96 hours after infection. ‘If we succeed in extending that timeline, we can also use these organoids to study chronic diseases such as chronic viral hepatitis and inflammatory bowel disease.’ They also hope to add other types of immune cells to the organoids at a later stage.