Different Responsiveness of Endothelial Cells to Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Added to Culture Media Under Gravity and Simulated Microgravity

Daniela Grimm, Johann Bauer, Claudia Ulbrich, Krist Westphal, Markus Wehland, Manfred Infanger, Ganna Aleshcheva, Jessica Pietsch, Myriam Ghardi, Michaël Beck, Houssein El Saghire, Louis de Saint-Georges, Sarah Baatout

    Research outputpeer-review


    When incubated under simulated microgravity (s-mg), endothelial cells (EC) form tubular structures that resemble vascular intimas. This delayed formation of 3D EC structures begins between the 5th and 7th day of culturing EC under conditions of s-mg. With the aim of learning about this initial phase of tubular structure formation, NFkBp65 protein content was similar in all cell populations, but gene and protein expression of phosphokinase A catalytic subunit, phosphokinase Ca, and extracellular signal-regulated kinases 1 and 2 was altered in cells cultured under s-mg. In contrast to controls, the 7-day-old s-mg cultures contained 3D aggregates with proliferating cells, enhanced numbers of necrotic cells, and osteopontin-negative EC as well as supernatants with reduced quantities of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble TNFRSF5, TNFSF5, intercellular adhesion molecule-1, tumor necrosis factor receptor 2, IL-18, complement C3, and von Willebrand factor. VEGF and=or bFGF (10 ng=mL) application influenced the accumulation of proteins in supernatants more profoundly under 1 g than under s-mg. These findings provide evidence that phosphokinase Ca plays a key role in tube formation. Improving the interaction of VEGF and=or bFGF with EC under s-mg could enhance the engineering of vascular intimas.
    Original languageEnglish
    Pages (from-to)1559-1573
    JournalTissue Engineering Part A
    Issue number5
    StatePublished - 4 May 2010

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