Growth of Endothelial Cells in Space and in Simulated Microgravity – a Comparison on the Secretory Level

Marcus Krüger, Jessica Pietsch, Johann Bauer, Sascha Kopp, Markus Wehland, Daniel T.O. Carvalho, Sarah Baatout, Marjan Moreels, Daniela Melnik, Markus Wehland, Marcel Egli, Jayashree Sahana, Sara Dam Kobbero, Thomas J. Corydon, Stefano Nebuloni, Manfred Infanger, Matthias Evert, Samuel Gass, Daniela Grimm

    Research outputpeer-review


    Background/Aims: Endothelial cells exposed to the Random Positioning Machine (RPM) reveal three different phenotypes. They grow as a two-dimensional monolayer and form three-dimensional (3D) structures such as spheroids and tubular constructs. As part of the ESA-SPHEROIDS project we want to understand how endothelial cells (ECs) react and adapt to long-term microgravity. Methods: During a spaceflight to the International Space Station (ISS) and a subsequent stay onboard, human ECs (EA.hy926 cell line) were cultured for 12 days in real microgravity inside an automatic flight hardware, specially designed for use in space. ECs were cultivated in the absence or presence of vascular endothelial growth factor, which had demonstrated a cell-protective effect on ECs exposed to an RPM simulating microgravity. After cell fixation in space and return of the samples, we examined cell morphology and analyzed supernatants by Multianalyte Profiling technology. Results: The fixed samples comprised 3D multicellular spheroids and tube-like structures in addition to monolayer cells, which are exclusively observed during growth under Earth gravity (1g). Within the 3D aggregates we detected enhanced collagen and laminin. The supernatant analysis unveiled alterations in secretion of several growth factors, cytokines, and extracellular matrix components as compared to cells cultivated at 1g or on the RPM. This confirmed an influence of gravity on interacting key proteins and genes and demonstrated a flight hardware impact on the endothelial secretome. Conclusion: Since formation of tube-like aggregates was observed only on the RPM and during spaceflight, we conclude that microgravity may be the major cause for ECs’ 3D aggregation.
    Original languageEnglish
    Pages (from-to)1039-1060
    Number of pages22
    JournalCellular Physiology and Biochemistry
    StatePublished - 17 Jan 2019

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