Severe acute viral diseases, such as cute hepatitis E caused by HEV infection, have prominent features of pathological inflammation that leads to tissue damage in patients. Macrophages have been recognized as an immune cell type important in orchestrating such hyperinflammation. The group of Qiuwei Abdullah Pan from Erasmus Medical Center in the Netherlands previously established human liver organoid-based models for HEV infection (Science Advances, 2022). Because these mini-organs do not contain immune cells, it remains difficult to use them to study immune response to a viral infection.
Now Dr. Pan’s group has succeeded in adding immune cells to organoids of the liver and intestine. They chose macrophages because those immune cells play a crucial role in inflammation. In macrophage-augmented liver organoids, challenge with HEV particles resulted in productive infection, inflammatory response and cell death. Thus, the macrophage integrated organoids make it easier to study hepatitis E disease manifestations more closely.
“This is important because it is usually not only the infection itself but often the subsequent excessive inflammatory response that is pathogenic.”
The team 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.
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.
Read the full articles:
Nature Biomedical Engineering. 2025 Jun 13. DOI: 10.1038/s41551-025-01417-5
Nature Communications. 2025 May 14;16(1):4475. DOI: 10.1038/s41467-025-59639-9
