Environmental oxygen affects ex vivo growth and proliferation of mesenchymal progenitors by modulating mitogen-activated protein kinase and mammalian target of rapamycin signaling.

Abstract

Stem and progenitor cells of hematopoietic and mesenchymal lineages reside in the bone marrow under low oxygen (O₂) saturation. O₂ levels used in ex vivo expansion of multipotent mesenchymal stromal cells (MSCs) affect proliferation, metabolism and differentiation. Using cell-based assays and transcriptome and proteome data, the authors compared MSC cultures simultaneously grown under a conventional 19.95% O₂ atmosphere or at 5% O₂. In 5% O₂, MSCs showed better proliferation and higher self-renewal ability, most probably sustained by enhanced signaling activity of mitogen-activated protein kinase and mammalian target of rapamycin pathways. Non-oxidative glycolysis-based energy metabolism supported growth and proliferation in 5% O₂ cultures, whereas MSCs grown under 19.95% O₂ also utilized oxidative phosphorylation. Cytoprotection mechanisms used by cells under 5% O_₂ differed from 19.95% O_₂  suggesting differences in the triggers of cell stress between these two O_₂  conditions. Based on the potential benefits for the growth and metabolism of MSCs, the authors propose the use of 5% O₂ for MSC culture.