Abstract
Hypoxia is characterized as insufficient oxygen delivery to tissues and cells in the body and is prevalent in many human physiology processes and diseases. Thus, it is an attractive state to experimentally study to understand its inner mechanisms as well as to develop and test therapies against pathological conditions related to hypoxia. Animal models in vivo fail to recapitulate some of the key hallmarks of human physiology, which leads to human cell cultures; however, they are prone to bias, namely when pericellular oxygen concentration (partial pressure) does not respect oxygen dynamics in vivo. A search of the current literature on the topic revealed this was the case for many original studies pertaining to experimental models of hypoxia in vitro. Therefore, in this review, we present evidence mandating for the close control of oxygen levels in cell culture models of hypoxia. First, we discuss the basic physical laws required for understanding the oxygen dynamics in vitro, most notably the limited diffusion through a liquid medium that hampers the oxygenation of cells in conventional cultures. We then summarize up-to-date knowledge of techniques that help standardize the culture environment in a replicable fashion by increasing oxygen delivery to the cells and measuring pericellular levels. We also discuss how these tools may be applied to model both constant and intermittent hypoxia in a physiologically relevant manner, considering known values of partial pressure of tissue normoxia and hypoxia in vivo, compared to conventional cultures incubated at rigid oxygen pressure. Attention is given to the potential influence of three-dimensional tissue cultures and hypercapnia management on these models. Finally, we discuss the implications of these concepts for cell cultures, which try to emulate tissue normoxia, and conclude that the maintenance of precise oxygen levels is important in any cell culture setting.
Highlights
Oxygen first began to significantly accumulate in the Earth’s atmosphere with the advent of photosynthesis, a process enabling the ancestors of cyanobacteria to obtain hydrogen from water and combine it with atmospheric CO2 to produce hydrocarbon molecules [1, 2]
The medium height and cell oxygen consumption rate both determine pericellular oxygen concentration, and significantly affect contemporary cell culture research owing to the lack of standardization of media amount supplied to cells and the attention given to the differences in oxygen demand of different cell lines under various experimental conditions [17, 36]
The need to tailor experimental conditions of in vitro hypoxia, namely O2 levels, to meet those found in living patients is further purported by mechanisms occurring in hypoxia at cellular and molecular levels, many of which are directly involved in disease pathophysiology
Summary
Specialty section: This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology. Animal models in vivo fail to recapitulate some of the key hallmarks of human physiology, which leads to human cell cultures; they are prone to bias, namely when pericellular oxygen concentration (partial pressure) does not respect oxygen dynamics in vivo. In this review, we present evidence mandating for the close control of oxygen levels in cell culture models of hypoxia. We discuss the basic physical laws required for understanding the oxygen dynamics in vitro, most notably the limited diffusion through a liquid medium that hampers the oxygenation of cells in conventional cultures. We discuss how these tools may be applied to model both constant and intermittent hypoxia in a physiologically relevant manner, considering known values of partial pressure of tissue normoxia and hypoxia in vivo, compared to conventional cultures incubated at rigid oxygen pressure.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
