3D spheroid culture in environmental toxicology

Spheroid culture has found applications in the field of environmental toxicology as a valuable tool for assessing the effects of environmental contaminants, pollutants, and chemicals on biological systems.

The spheroid cell culture approach provides several advantages for toxicological studies related to environmental exposure.

Physiological relevance

Spheroids better mimic the in vivo three-dimensional architecture and microenvironment of tissues compared to traditional two-dimensional cell cultures. This increased physiological relevance allows for more accurate assessments of how environmental toxins affect cellular responses.

Complexity and heterogeneity

Spheroids can consist of multiple cell types, including different cell lines or primary cells, enhancing their ability to replicate tissue complexity and cellular interactions. This is particularly valuable for studying toxic effects in organs composed of multiple cell types, such as the liver, lung, and kidney.

Drug metabolism and biotransformation

Spheroids, especially those derived from liver cells, can be used to assess the metabolism and biotransformation of environmental chemicals. This is crucial for evaluating how toxins are processed and detoxified within the body.

Biomarker discovery

Spheroid cultures allow researchers to identify and measure specific biomarkers associated with toxic responses. These biomarkers can serve as indicators of cellular stress, damage, or dysfunction caused by environmental toxins.

High-throughput screening

Miniaturized spheroids can be employed for high-throughput screening of environmental chemicals. This enables the rapid evaluation of a large number of compounds, helping prioritize those with potential toxicity for further investigation.

Toxicity pathways and mechanisms: Spheroid culture facilitates the study of specific toxicity pathways and mechanisms underlying the adverse effects of environmental chemicals. This knowledge is essential for understanding how toxins disrupt normal cellular processes.

Environmental monitoring: Spheroid models may find applications in environmental monitoring, where they can be exposed to environmental samples to assess their toxic effects and identify potential hazards in the environment.

References

1. Antoni D, Burckel H, Josset E, Noel G. Three-dimensional cell culture: a breakthrough in vivo. Int J Mol Sci. 2015 Mar 11;16(3):5517-27. doi: 10.3390/ijms16035517. PMID: 25768338; PMCID: PMC4394490.

2. Białkowska K, Komorowski P, Bryszewska M, Miłowska K. Spheroids as a Type of Three-Dimensional Cell Cultures-Examples of Methods of Preparation and the Most Important Application. Int J Mol Sci. 2020 Aug 28;21(17):6225. doi: 10.3390/ijms21176225. PMID: 32872135; PMCID: PMC7503223.

3. Antoni D, Burckel H, Josset E, Noel G. Three-dimensional cell culture: a breakthrough in vivo. Int J Mol Sci. 2015 Mar 11;16(3):5517-27. doi: 10.3390/ijms16035517. PMID: 25768338; PMCID: PMC4394490.

4. Fey SJ, Wrzesinski K. Determination of drug toxicity using 3D spheroids constructed from an immortal human hepatocyte cell line. Toxicol Sci. 2012 Jun;127(2):403-11. doi: 10.1093/toxsci/kfs122. Epub 2012 Mar 27. PMID: 22454432; PMCID: PMC3355318.

5. Karimi, H., Moskal, P., Żak, A. et al. 3D melanoma spheroid model for the development of positronium biomarkers. Sci Rep 13, 7648 (2023). https://doi.org/10.1038/s41598-023-34571-4

6. Hiemstra S, Ramaiahgari SC, Wink S, Callegaro G, Coonen M, Meerman J, Jennen D, van den Nieuwendijk K, Dankers A, Snoeys J, de Bont H, Price L, van de Water B. High-throughput confocal imaging of differentiated 3D liver-like spheroid cellular stress response reporters for identification of drug-induced liver injury liability. Arch Toxicol. 2019 Oct;93(10):2895-2911. doi: 10.1007/s00204-019-02552-0. Epub 2019 Aug 27. PMID: 31552476.

7. Hatherell S, Baltazar MT, Reynolds J, Carmichael PL, Dent M, Li H, Ryder S, White A, Walker P, Middleton AM. Identifying and Characterizing Stress Pathways of Concern for Consumer Safety in Next-Generation Risk Assessment. Toxicol Sci. 2020 Jul 1;176(1):11-33. doi: 10.1093/toxsci/kfaa054. PMID: 32374857; PMCID: PMC7357173.