In an article published in the scientific journal Nature Microbiology, scientists from Rotterdam and Leiden describe how they generate skin organoids from stem cells, and use them for modeling mpox virus infection. An organoid is a complex three-dimensional structure. Like real human skin, a skin organoid consists of multiple layers and different cell types, and sometimes even hair.
The researchers conclude that skin organoids are very suitable for studying mpox. Under the leadership of translational researcher Dr. Pengfei Li from Erasmus MC, they infected the organoids with the mpox virus. ‘The virus can infect the cells of the organoids, produce new virus particles, and infect new cells. These are the same steps as in the infection of real skin’, says Li. The researchers also observed that treating the infected skin organoids with the antiviral drug tecovirimat inhibits the production of virus particles. Tecovirimat is authorised in the EU for the treatment of mpox.
What is mpox?
Mpox, formerly known as monkeypox, is a disease that primarily occurs in West Africa and Central Africa. In 2022, the disease was diagnosed in people in Europe and America, areas where the disease was not originally found. The virus mainly infects the skin, causing blisters, bumps, or spots.
Until now, research on mpox has mainly been conducted using cell lines and animal models. ‘These have various limitations, both biologically and ethically. Organoids do not have these limitations’, says Li. The researchers expect that organoids will be used to learn more about how the body responds to infection with the mpox virus and serve as a model for testing new drugs.
The latter is not only important for mpox, according to the researchers. ‘There are still various other poxviruses, siblings of mpox, that can potentially cross over from animals to humans at any time. Models like skin organoids are essential to be prepared for new pandemics and quickly find new treatments’, says Li. The newly established research group of Dr. Li is now exploring organoid technology for modeling many other viral diseases, especially the ones affecting the gut-liver axis. His research ambition is to understand the pathogenesis and develop innovative therapeutic strategies. He has particular interest in using human liver and intestinal organoids for studying the infections of enteric and hepatitis viruses.
This study is a collaboration of researchers from Erasmus MC, Leiden University Medical Center, and the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW). The study leaders are Karine Raymond (LUMC, reNEW) and Qiuwei Abdullah Pan (Erasmus MC).