Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Should culture media for microphysiological systems be nutritionally physiological?

The incipient use of microphysiological systems (MPSs) in the drug regulatory pathway is based on equivalent or superior predictive value in the evaluation of drug efficacy, safety and toxicology, compared with other novel alternative methods (NAMs) or animal studies. Current MPS practice is not deploying available physiological culture media solutions. Will the clinical translational reliability of MPSs be potentially compromised by the use of hyper-nutritional media?

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

References

  1. Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P. & Tagle, D. A. Organs-on-chips: into the next decade. Nat. Rev. Drug. Discov. 20, 345–361 (2021).

    Article  Google Scholar 

  2. Stewart, A., Denoyer, D., Gao, X. & Toh, Y. C. The FDA modernisation act 2.0: Bringing non-animal technologies to the regulatory table. Drug. Discov. Today 28, 103496 (2023).

    Article  Google Scholar 

  3. Zhang, X. et al. Nutritionally physiological cell culture medium and 3D culture influence breast tumour proteomics and anti-cancer drug effectiveness. Pharmacol. Res. 210, 107519 (2024).

    Article  Google Scholar 

  4. Vande Voorde, J. et al. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Sci. Adv. 5, eaau7314 (2019).

    Article  Google Scholar 

  5. Cantor, J. R. et al. Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase. Cell 169, 258–272.e217 (2017).

    Article  Google Scholar 

  6. Yang, Y. et al. Dual-purpose aptamer-based sensors for real-time, multiplexable monitoring of metabolites in cell culture media. ACS Nano 18, 26127–26139 (2024).

    Google Scholar 

  7. Gardner, G. L. et al. Rapid nutrient depletion to below the physiological range by cancer cells cultured in Plasmax. Am. J. Physiol. Cell Physiol. 323, C823–C834 (2022).

    Article  Google Scholar 

  8. Gao, X., Wu, Y., Cheng, T. & Stewart, A. G. Comprehensive multiplexed superfusion system enables physiological emulation in cell culture: exemplification by persistent circadian entrainment. Lab. Chip 22, 1137–1148 (2022).

    Article  Google Scholar 

  9. Gardner, G. L. & Stuart, J. A. Tumor microenvironment-like conditions alter pancreatic cancer cell metabolism and behavior. Am. J. Physiol. Cell Physiol. 327, C959–C978 (2024).

    Article  Google Scholar 

  10. Fischer, M. Physiological media advance cell culture experiments. Trends Biochem. Sci. 48, 103–105 (2023).

    Article  Google Scholar 

Download references

Acknowledgements

The authors report grant support from ARC IC170100016.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alastair G. Stewart.

Ethics declarations

Competing interests

A.G.S. and B.G. are co-inventors of the RPM22 and multiplexed biosensor systems discussed in this Comment.

Peer review

Peer review information

Nature Reviews Bioengineering thanks Jeff Stuart, who co-reviewed with Ricardo Alva, Saverio Tardito, and Martin Fischer for their contribution to the peer review of this work.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stewart, A.G., Gunatilaka, A. & Gao, B. Should culture media for microphysiological systems be nutritionally physiological?. Nat Rev Bioeng 3, 357–358 (2025). https://doi.org/10.1038/s44222-025-00290-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s44222-025-00290-w

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research