Hans Snoeck: Viral modeling using hPSC-derived lung organoids

 By: Arooba Ahmed (CC '23)
    
      Dr. Snoeck’s lab is working to develop organoids, which are tiny, self-organized three-dimensional tissue cultures that are derived from stem cells. They can make lung organoids from lung embryonic stem cells. 
     There are two stages of the organoids. First, there are lung bud organoids in suspension culture, which can be put in kidney capsules of mice or in matrigels (a protein mixture) to develop further. Within the suspension culture, they undergo human lung development with human airways and specifications as demonstrated by distal markers and surfactant proteins (which are the same as what you see in humans). They are Collaborating with another lab to use this to model COVID-19 in humanized mice. The organoids match with human fetal lungs, so they will infect it with COVID -19 to see tropism of the virus.
     They have been also modelling genetic susceptibility to influenza and respiratory syncytial virus (RSV), which has high morbidity worldwide. In RSV, infected cells become stuffed into small airways, and they saw this in how the infected cells sloughed into the lumens of the organoids after just two days of infection.
     In addition to making the organoids available for disease modelling, they want to use them to research how to prevent and treat lung complications. The tips of the organoids have plenty of type 2 cells, a special type of cell in the alveoli in the lungs, which makes it a great research tool. For example, they have obtained fibrotic organoids by mutating proteins involved in surfactant production. This will help to study interstitial lung disease, which could occur in those patients recovering from COVID-19 (as what happened with the SARS epidemic). 
     They can develop organoids for in vitro modelling, drug testing, and modelling individual susceptibility. However, the limitation is that there are no blood vessels or innate immune cells in the organoids. However, they are trying to introduce macrophages and have also generated vascular organoids that they are trying to integrate with lung organoids.