1. Environmental oxygen affects ex vivo growth and proliferation of mesenchymal progenitors by modulating mitogen-activated protein kinase and mammalian target of rapamycin signaling.
- Author
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da Graça Cabreira M, Wang X, Critsinelis A, Setegne M, Lotfi P, Wan YW, Barrios G, Mei Z, Gee AP, Buja LM, and Perin E
- Subjects
- Cells, Cultured, Sirolimus, Cell Proliferation, Cell Differentiation physiology, TOR Serine-Threonine Kinases, Oxygen metabolism, Mitogen-Activated Protein Kinases
- Abstract
Background Aims: Stem and progenitor cells of hematopoietic and mesenchymal lineages reside in the bone marrow under low oxygen (O
2 ) 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 2 2 2 for MSC culture., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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