Oxygen toxicity: cellular mechanisms in normobaric hyperoxia

Alva, Ricardo; Mirza, Maha; Baiton, Adam; Lazuran, Lucas; Samokysh, Lyuda; Bobinski, Ava; Cowan, Cale; Jaimon, Alvin; Obioru, Dede; Makhoul, Tala Al; Stuart, Jeffrey A.

doi:10.1007/s10565-022-09773-7

Cited by 23 publications

(7 citation statements)

References 358 publications

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“…LDH is an enzyme released by cells when the cell membrane suffers damage and is indicative of cell death or cytotoxicity. 48 An increase of LDH activity was observed in OGM4 and OGM5 scaffolds, further supporting that a threshold of dissolved oxygen must be met for optimum cell growth and function. The OGM3 scaffolds exhibited the least amount of LDH activity, indicating that OGM3 may be the most suitable scaffold composition for the H9c2 cardiomyocytes.…”

Section: Cytotoxicity Analysis Within Oxygen-generating Scaffolds Via...mentioning

confidence: 82%

Oxygen-Generating Scaffolds for Cardiac Tissue Engineering Applications

Suvarnapathaki

Nguyen

Goulopoulos

et al. 2022

ACS Biomater. Sci. Eng.

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Homogeneous vascularization of implanted tissue constructs can extend to 5 weeks, during which cell death can occur due to inadequate availability of oxygen. Researchers are engineering biomaterials that generate and release oxygen in a regulated manner, in an effort to overcome this hurdle. A main limitation of the existing oxygen-generating biomaterials is the uncontrolled release of oxygen, which is ultimately detrimental to the cells. This study demonstrates the incorporation of calcium peroxide (CaO 2 ) within a hydrophobic polymer, polycaprolactone (PCL), to yield composite scaffolds with controlled oxygen release kinetics sustained over 5 weeks. Oxygen-generating microparticles coencapsulated with cardiomyocytes in a gelatin-based hydrogel matrix can serve as model systems for cardiac tissue engineering. Specifically, the results reveal that the oxygen-generating microspheres significantly improve the scaffold mechanical strength ranging from 5 kPa to 35 kPa, have an average scaffold pore size of 50−100 μm, swelling ratios of 33.3−29.8%, and degradation with 10−49% remaining mass at the end of a 48 h accelerated enzymatic degradation. The oxygen-generating scaffolds demonstrate improvement in cell viability, proliferation, and metabolic activity compared to the negative control group when cultured under hypoxia. Additionally, the optimized oxygen-generating constructs display no cytotoxicity or apoptosis. These oxygen-generating scaffolds can possibly assist the in vivo translation of cardiac tissue constructs.

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Section: Cytotoxicity Analysis Within Oxygen-generating Scaffolds Via...mentioning

confidence: 82%

Oxygen-Generating Scaffolds for Cardiac Tissue Engineering Applications

Suvarnapathaki

Nguyen

Goulopoulos

et al. 2022

ACS Biomater. Sci. Eng.

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“…As explained at the beginning, the tissue-relevant oxygen concentration (physioxia) plays a crucial role in cell culture. Cell culture experiments are often performed under ambient atmosphere, which corresponds to an oxygen concentration of 18.6% in the standard incubator with 5% CO 2 ( Wenger et al, 2015 ; Alva et al, 2022b ). However, this is in no way comparable to physiological conditions and can lead to hyperoxia.…”

Section: Discussionmentioning

confidence: 99%

O2-sensitive microcavity arrays: A new platform for oxygen measurements in 3D cell cultures

Grün

Pfeifer

Liebsch

et al. 2023

Front. Bioeng. Biotechnol.

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Oxygen concentration plays a crucial role in (3D) cell culture. However, the oxygen content in vitro is usually not comparable to the in vivo situation, which is partly due to the fact that most experiments are performed under ambient atmosphere supplemented with 5% CO2, which can lead to hyperoxia. Cultivation under physiological conditions is necessary, but also fails to have suitable measurement methods, especially in 3D cell culture. Current oxygen measurement methods rely on global oxygen measurements (dish or well) and can only be performed in 2D cultures. In this paper, we describe a system that allows the determination of oxygen in 3D cell culture, especially in the microenvironment of single spheroids/organoids. For this purpose, microthermoforming was used to generate microcavity arrays from oxygen-sensitive polymer films. In these oxygen-sensitive microcavity arrays (sensor arrays), spheroids cannot only be generated but also cultivated further. In initial experiments we could show that the system is able to perform mitochondrial stress tests in spheroid cultures to characterize mitochondrial respiration in 3D. Thus, with the help of sensor arrays, it is possible to determine oxygen label-free and in real-time in the immediate microenvironment of spheroid cultures for the first time.

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“…These results are consistent with a previous study showing little overlap in the proteome of three diffuse large B-cell lymphoma cell lines cultured in the same two O 2 conditions [ 76 ]. Increased oxidative stress associated with higher O 2 levels affects a variety of pathways, including the p53 pathway and mitogen-activated protein kinase (MAPK) pathways (reviewed in [ 77 ]). Given their different origins and genetic backgrounds, cancer cells have distinct mutations, including gene copy number differences, of genes related to these pathways.…”

Section: Discussionmentioning

confidence: 99%

Culture of Cancer Cells at Physiological Oxygen Levels Affects Gene Expression in a Cell-Type Specific Manner

et al. 2022

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Standard cell culture is routinely performed at supraphysiological oxygen levels (~18% O2). Conversely, O2 levels in most mammalian tissues range from 1–6% (physioxia). Such hyperoxic conditions in cell culture can alter reactive oxygen species (ROS) production, metabolism, mitochondrial networks, and response to drugs and hormones. The aim of this study was to investigate the transcriptional response to different O2 levels and determine whether it is similar across cell lines, or cell line-specific. Using RNA-seq, we performed differential gene expression and functional enrichment analyses in four human cancer cell lines, LNCaP, Huh-7, PC-3, and SH-SY5Y cultured at either 5% or 18% O2 for 14 days. We found that O2 levels affected transcript abundance of thousands of genes, with the affected genes having little overlap between cell lines. Functional enrichment analysis also revealed different processes and pathways being affected by O2 in each cell line. Interestingly, most of the top differentially expressed genes are involved in cancer biology, which highlights the importance of O2 levels in cancer cell research. Further, we observed several hypoxia-inducible factor (HIF) targets, HIF-2α targets particularly, upregulated at 5% O2, consistent with a role for HIFs in physioxia. O2 levels also differentially induced the transcription of mitochondria-encoded genes in most cell lines. Finally, by comparing our transcriptomic data from LNCaP and PC-3 with datasets from the Prostate Cancer Transcriptome Atlas, a correlation between genes upregulated at 5% O2 in LNCaP cells and the in vivo prostate cancer transcriptome was found. We conclude that the transcriptional response to O2 over the range from 5–18% is robust and highly cell-type specific. This latter finding indicates that the effects of O2 levels are difficult to predict and thus highlights the importance of regulating O2 in cell culture.

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Oxygen toxicity: cellular mechanisms in normobaric hyperoxia

Cited by 23 publications

References 358 publications

Oxygen-Generating Scaffolds for Cardiac Tissue Engineering Applications

Oxygen-Generating Scaffolds for Cardiac Tissue Engineering Applications

O2-sensitive microcavity arrays: A new platform for oxygen measurements in 3D cell cultures

Culture of Cancer Cells at Physiological Oxygen Levels Affects Gene Expression in a Cell-Type Specific Manner

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