For many decades, cell lines have been cultured in standard CO2 incubators at “normal” atmospheric oxygen concentrations of about 21%. But oxygen concentrations in the human or animal body are much lower, varying from as low as 1-2 % up to about 12%, depending on the tissue microenvironment. Oxygen concentration affects metabolism, proliferation, differentiation, disease progression and more. Controlling oxygen in vitro is increasingly important in biological function and disease modeling, pharmaceutical development and production, cell therapy, and of course in culturing stem cells. Creating hypoxia is critical to maintain pluripotency, control differentiation, limit oxidative damage and more. In this talk, we:

• Review history and advances in understanding oxygen concentration in vivo and how hypoxia-inducible factor-1 (HIF-1) modulates the cell’s response.
• Present examples demonstrating the effects of hypoxia on stem cells and primary cells, including better cell growth, less differentiation and less oxidative damage.
• Explain how “tri-gas” CO2 incubators provide a physiological oxygen environment.