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

Published:September 13, 2022DOI:https://doi.org/10.1016/j.jcyt.2022.06.005

      Abstract

      Background aims

      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.

      Methods

      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.

      Results

      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% O2 differed from 19.95% O2  suggesting differences in the triggers of cell stress between these two O2  conditions.

      Conclusions

      Based on the potential benefits for the growth and metabolism of MSCs, the authors propose the use of 5% O2 for MSC culture.

      Key Words

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