Activity and function of auxiliary fluxes of glucose metabolism in response to physiological normoxia (5 % O2) during long-term Adipose-Derived Stem/Stromal cell culture

• DOI: 10.1016/j.ejcb.2025.151486
• Publication Date: 2025-03-30T22:09:34Z
• Authors: Paulina Rybkowska; Maria Kawalec; Dorota Dymkowska; Klaudia Radoszkie...; Barbara Zabłocka; Krzysztof Zabłocki; Anna Sarnowska

Energy metabolism homeostasis emerges as a dominant element influencing mesenchymal stem/stromal cells' trajectory of development. The predominant glycolysis activity is primary driver cell proliferation and maintenance the high-energetic state. Here, we examined functions two crucial auxiliary pathways: phosphate-pentose pathway (PPP) fructose-2,6-biphosphate (FBP) to evaluate their impact on therapeutic potential Adipose-Derived Stem/Stromal cells (ASCs) during prolonged culture in various oxygen conditions: 5 % O2 - physiological normoxia or 21 atmospheric oxygen. Our findings demonstrate that ASCs cultured increased rate proliferation, migration, expression stemness factors, which prominent initial middle passages. Additionally, exhibited heightened protection mechanisms against free radicals, LDH gene expression, elevated extracellular acidification (ECAR). By estimating HIF-1α level, concluded conditions were insufficient induce profound hypoxic state ASCs. However, at protein both PPP FBP pathways appeared be more active young (2-passage) cells, regardless conditions, diminished over time. chemical suppression G6PDH by Polydatin inhibition PFKFB3 PFK-158 (passage-2) revealed dose- time-dependent effect decreasing migratory capabilities cells. Nevertheless, our work underscores adaptable nature ASC prevailing external with aging contributing decline glycolysis-associated pathways.