Simulated microgravity modulates the mesenchymal stromal cell response to inflammatory stimulation

Abstract

The duration and distance of manned space flights emphasizes the importance of advanced elucidation of space flight factors and their effects on human beings. The exposure to inflammatory mediators under microgravity may contribute to the activity of different cells, perivascular stromal cells (MSCs) in particular. Inflammatory activation is now considered as a principal cue of MSC engagement in reparative remodeling. In the present paper, the effect of simulated microgravity (sµg) on TNFα-mediated priming of adipose tissue-derived MSC (ASCs) was examined. Sµg per se did not induce inflammatory-related changes, such as elevation of ICAM-1 and HLA-ABC expression, soluble mediator production, or shifting of the transcription profile in ASCs. Moreover, the attenuated ASC response to TNFα priming under sµg was manifested in decreased production of TNFα-dependent pleiotropic cytokines (IL-8 and MCP-1), matrix remodeling proteases, and downregulation of some genes encoding growth factors and cytokines. Time-dependent analysis detected the first signs of priming attenuation after 48 hours of 3D-clinorotation. A reduced response of MSCs to priming under sµg can be a negative factor in terms of MSC involvement in tissue remodeling processes.

Guest Edited Collection: Gravitational biology and space medicine

“…Several studies investigating the impact of µ g on the behaviour and health of mice on the ISS were published in this Collection 18–23 , in addition to investigations at the cellular level in space 24 and in short-term µ g provided by PF maneuvers 25 . Moreover, cell studies in simulated (s-) µ g at ground-based facilities are included in this Collection 26–30 .…”

“…3D clinorotation was used to study mesenchymal stromal cell (MSC) response to inflammatory stimulation 26 . A reduced response of MSCs to priming in µ g might also indicate less involvement of these cells in tissue remodelling 26 . Arun et al .…”

Microglial activation in spaceflight and microgravity: potential risk of cognitive dysfunction and poor neural health

“…Several studies have reported that c-fos and c-Jun are regulated in simulated microgravity ( Shi et al, 2021 ). Furthermore, ICAM-1, a transmembrane protein expressed on the surface of epithelial cells, endothelial cells, T cells, and macrophages, was also demonstrated to respond to microgravity stimulation ( Buravkova et al, 2018 ; Lü et al, 2019 ; Nassef et al, 2019 ; Ratushnyy et al, 2019 ). ICAM-1 expression was observed to decrease quickly and reversibly on the surface of BV-2 cells following the microgravity phase in parabolic flight, but in long-term microgravity induced by orbital SIMBOX/Shenzhou-8, ICAM-1 expression increased in macrophage-like differentiated human U937 cells ( Paulsen et al, 2015 ).…”

Immunity in Space: Prokaryote Adaptations and Immune Response in Microgravity

“…Other immune responses are also affected by a low-shear environment; inflammation, specifically adaptation of the vasculature (release of vasoactive factors [119]), is determined by the vessel wall state which composes of endothelial cells and mesenchymal stem cells [120]. Microgravity analogues have been shown to exacerbate the effect of endothelial cell activation by inflammatory mediators [121].…”