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Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells
Department of Experimental Oncology, European Institute of Oncology, Via Adamello16, 20139 Milan, Italy
Present address: Center of Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain
* Author to whom correspondence should be addressed.
Received: 21 November 2012; in revised form: 4 January 2013 / Accepted: 5 January 2013 / Published: 22 January 2013
Abstract: Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2) conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.
Keywords: hypoxia; mesenchymal stem cells; differentiation; oxygen; bone marrow stromal cells
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Berniakovich, I.; Giorgio, M. Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells. Int. J. Mol. Sci. 2013, 14, 2119-2134.
Berniakovich I, Giorgio M. Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells. International Journal of Molecular Sciences. 2013; 14(1):2119-2134.
Berniakovich, Ina; Giorgio, Marco. 2013. "Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells." Int. J. Mol. Sci. 14, no. 1: 2119-2134.