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.
Highlights
The proportion of living cells (PI-) in the AnnV-PI test did not differ between the experimental groups and was more than 95%
After TNFα exposure, we have demonstrated a significant elevation of some adipose tissue perivascular MSCs (ASCs) growth factors: pigment epithelium-derived factor (PEDF) (Fig. 2B), insulin-like growth factor-1 (IGF-1), transforming growth factor β (TGF-β) (Fig. 3A)
Dysregulation of various cell system functions is one of the main negative effects caused by space flight factors
Summary
A reduced response of MSCs to priming under sμg can be a negative factor in terms of MSC involvement in tissue remodeling processes. To simulate the effects of microgravity on adherent cells, 2D- and 3D-clinorotation (random positioning machine (RPM)) are considered the most appropriate[12,13] These models have shown that ECs demonstrate both early and delayed responses[9,10,11,14,15]. The effect of microgravity on cells of the stromal lineage, MSCs in particular, is currently being considered primarily due to their potential for differentiation, production of soluble mediators, and involvement in bone www.nature.com/scientificreports/. TNFα+/TNFα− -ASCs were cultured with/without TNFα. sμg/1 g - simulated microgravity/control
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