Earlier you mentioned three-dimensional cell cultures. Can you briefly describe what these look like, how they are set up and how they develop?
Grimm: Adherent cells typically form a two-dimensional cell layer in the laboratory. This monolayer grows on the bottom of a culture flask. In space or simulated microgravity settings, individual cells detach after a period of about twelve to twenty hours, depending on the cell type. Initially, these are just individual cells but then there are continuously more and more cells that do so. These detached cells form spherical aggregates. The main difference between them and the structures formed under static 1g conditions is that the space aggregates can become larger, last longer and don’t exhibit necrosis. The major drawback of laboratory experiments is the fact that lab-created cell structures grow well for up to three weeks, then reach a plateau and ultimately die after four or five weeks. The spheroids that we grow in space are perfectly suited to test drugs thanks to their longevity. For example, the aggregates that formed in space in 2011 were five times bigger than lab-created spheroids. On another flight in 2014, there was no spheroid formation because the flight was delayed several times to where we were ultimately forced to send confluent cells into space that formed an extracellular matrix and did not detach. Having said that, we were also able to discover many secretory proteins during this event, which are of interest for further research and drug development.
A variety of factors are responsible for spheroid formation in zero gravity conditions. We know that the epidermal growth factor and the connective tissue growth factor of cells play a role. What’s more, many proteins that are essential for cell adhesion are also heavily involved in this process. We have published our initial findings in the Scientific Reports journal, among others. We also used breast cancer cells for this research.
Are there any other research approaches that use a zero gravity environment?
Grimm: In the coming months, we will take part in the 31st Parabolic Flight Campaign of the German Aerospace Center (Deutsches Zentrum für Luft- und Raumfahrt). We are preparing for further research in Bordeaux-Mérignac during the last week of February. The breast cancer cells will be subjected to thirty-one parabolas during each flight, while we will study early gene expression and cytoskeletal changes under real microgravity conditions. Starting April 15, team members of my working group will also travel to Kiruna in the north of Sweden to study transfected breast cancer cells using a microscope for six minutes in zero gravity conditions.
I am also working at the Aarhus University. As part of this endeavor, a project that focuses on wound healing in space is planned for 2022. The backdrop is that more and more people can be sent into space, thus resulting in increasing skin injuries. We study the wound healing process on an ex vivo skin model. We are currently still in the preparation phase and study wound healing in a simulated zero gravity environment by collaborating with Professor Monica Monici, University of Florence in Italy and Professor Mandred Infanger of the Clinic for Plastic, Aesthetic and Hand Surgery at the Otto von Guericke University Magdeburg. This research could later also be generally applied in regenerative medicine.