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Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans
Open accessAbstract
The extensive oxygen gradient between the air we breathe (Po 2 ~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 O 2 levels in which to culture cells, coupled with a lack of the technology to replicate and maintain a physiological O 2 environment in vitro, has hindered addressing this issue thus far. In this review, we aim to address the current understanding of tissue Po 2 distribution in vivo and summarize the attempts made to replicate these conditions in vitro. The state-of-the-art techniques employed to accurately determine O 2 levels, as well as the issues associated with reproducing physiological O 2 levels in vitro, are also critically reviewed. We aim to provide the framework for researchers to undertake cell culture under O 2 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.
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“It is known that native tissue oxygen concentrations can be between 1-5% (Ottosen et al., 2006; Wenger et al., 2015; Keeley and Mann, 2019).”
From Guidance document on Good cell and tissue culture practice 2.0 (GCCP 2.0) (2021) · cites this paper as Keeley and Mann, 2019
In the citing paper
“including human hepatocytes (Ng et al., 2014) and rat renal mesangial cells (Metzen et al., 1995), where perturbed O2 levels correlated with anomalous cellular responses (Keeley and Mann, 2019).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as Keeley and Mann, 2019
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Self-citation
Metadata
- Authors
- Keeley, T. P., & Mann, G. E.
- Affiliations
- King's College London (GB)
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2019-01-01
- Volume
- 99
- Issue
- 1
- Pages
- 161-234
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2804335534
- Cited by
- 329
- References
- 685
- Citations by year
- 2026: 38 · 2025: 47 · 2024: 57 · 2023: 53 · 2022: 51 · 2021: 32 · 2020: 31 · 2019: 19
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- British Heart Foundation (BHF) (FS/13/66/30445, PG/13/1/29801)
- Heart Research UK (NET RG2633)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Biomedical and Chemical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- tissue oxygen tension, oxygen gradients, oxygen toxicity
- MeSH terms
- Air, Animals, Cell Physiological Phenomena, Humans, Mitochondria, Oxygen, Oxygen Consumption, Models, Animal
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