O_2-influence on MMSC's metabolic and differentiation status

摘要

Multipotential mesenchymal stromal cells (MMSCs) are precursors with great cell renewal and several lineages differentiating potential. It is assumed now, that hypoxic conditions better mimic the natural microenvironment of these cells. We therefore isolated MMSCs from human adipose tissue and expanded them permanently under 20% and 1-3-5% O_2 to compare MMSCs functional and metabolic activity and gene expression profile. MMSCs rapidly adapted to decreased O_2 level switching on glucose metabolic pathway to anaerobic, accompanying by decline in mitochondrial transmembrane potential. Osteogenic differentiation was diminished in low O_2 and this effect was reversible. Analysis of genes expression revealed temporal change in the share of genes with altered expression (0,036%, 24h, 0,12% and 3,6% after 24h, 96h and permanent low O_2 respectively, the largest number of differentially expressed genes were revealed in groups related to AT-MMSCs properties mostly significantly attenuated in hypoxia, as proliferation and differentiation. The study demonstrated that low oxygen level in culture medium can serve as a factor attenuated the AT-MMSCs metabolism and commitment, which can be important for further basic and applied studies in cell biology and physiology