Monkeypox infection and drug treatment modelled in skin organoids made from human stem cells

Researchers from the lab of reNEW Leiden PI Karine Raymond, have successfully modeled monkeypox infections in human skin organoids. The results of the study, published in Nature Microbiology on October 12th, highlight the potential of human stem-cell derived skin organoids to model viral infections and test potential novel therapeutics.

The skin is the largest organ in the human body. When healthy and functioning properly, it creates a barrier and provides us protection from pathogens and other harmful effects from our environment. Examples of factors that challenge the protective function of the skin are microorganisms, UV radiation or genetic diseases.

One virus that causes skin problems in the form of lesions when it infects humans is the monkeypox or Mpox virus. Although it is endemic in certain regions in Africa, this virus caused a worldwide stir in 2022 when outbreaks occurred across the globe in non-endemic regions, with symptoms being more severe than those typically described by patients. Until now, research on Mpox virus had been carried out using cultured human cell lines or animal models. However, a more relevant model that is able to recapitulate key structural and functional features of human skin to study viral infections was lacking.

In the latest reNEW publication from the Raymond group, co-first author Spiros Pachis and collaborators from the Pan group at the Erasmus Medical Center in Rotterdam  show that the skin organoids they make are susceptible to infection by the Mpox virus and support the generation of new viruses with the ability to infect other cells. By using a technique called transmission electron microscopy they demonstrated that they could capture and visualize all stages that the Mpox virus goes through during its life cycle. Moreover, when they looked at the effects that the infection had on the expression of genes in the skin organoid cells, they observed extensive alterations compared to the healthy control cells. These included changes in some of the specific genes that encode for proteins with a structural or barrier function role in skin as well as molecules that skin cells normally produce when they are exposed to some form of stress. In a positive discovery, the researchers were able to confirm the effectiveness of a promising antiviral candidate drug against the Mpox virus. They found that administering it at different timepoints during the infection process significantly inhibited the production of new viruses and prevented the gene expression alterations from taking place.

This work is the first to demonstrate the use of the skin organoid model to study viral infection. Importantly, it shows that human skin organoids can reproduce effects that contribute to the pathogenicity of the Mpox virus in patients. This opens up exciting potential research avenues that aim to uncover more mechanistic insights on what takes place when the Mpox virus or other pathogens that affect the skin infect patients. Importantly, skin organoids can also serve as a platform to test new therapeutics. Ultimately, this study provides a clear translational application for skin organoids and highlights the overall potential that stem cell-derived advanced 3D models hold.

Doctor Karine RaymondreNEW PI Dr. Karine Raymond’s work aims at understanding how the cells in the skin sense and adapt to environmental stresses. Her lab at Leiden University Medical Center uses advanced skin-organoids, based on human induced pluripotent stem cells (hiPSCs), to model these processes. Read more on Karine Raymond’s group on our website:

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