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The extensive oxygen gradient between the air we breathe (Po2 ~21 kPa) and its ultimate distribution within mitochondria (as low as ~0.5-1 kPa) is testament to the efforts expended in limiting its inherent toxicity. It has long been recognized that cell culture undertaken under room air conditions falls short of replicating this protection in vitro. Despite this, difficulty in accurately determining the appropriate O2 levels in which to culture cells, coupled with a lack of the technology to replicate and maintain a physiological O2 environment in vitro, has hindered addressing this issue thus far. In this review, we aim to address the current understanding of tissue Po2 distribution in vivo and summarize the attempts made to replicate these conditions in vitro. The state-of-the-art techniques employed to accurately determine O2 levels, as well as the issues associated with reproducing physiological O2 levels in vitro, are also critically reviewed. We aim to provide the framework for researchers to undertake cell culture under O2 levels relevant to specific tissues and organs. We envisage that this review will facilitate a paradigm shift, enabling translation of findings under physiological conditions in vitro to disease pathology and the design of novel therapeutics.

Original publication

DOI

10.1152/physrev.00041.2017

Type

Journal article

Journal

Physiological reviews

Publication Date

01/2019

Volume

99

Pages

161 - 234

Addresses

King's British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, Faculty of Life Sciences and Medicine, King's College London , London , United Kingdom.

Keywords

Mitochondria, Animals, Humans, Oxygen, Models, Animal, Air, Oxygen Consumption, Cell Physiological Phenomena