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Standardizing designed and emergent quantitative features in microphysiological systems

Nature Biomedical Engineering volume 8, pages 941–962 (2024)Cite this article

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Abstract

Microphysiological systems (MPSs) are cellular models that replicate aspects of organ and tissue functions in vitro. In contrast with conventional cell cultures, MPSs often provide physiological mechanical cues to cells, include fluid flow and can be interlinked (hence, they are often referred to as microfluidic tissue chips or organs-on-chips). Here, by means of examples of MPSs of the vascular system, intestine, brain and heart, we advocate for the development of standards that allow for comparisons of quantitative physiological features in MPSs and humans. Such standards should ensure that the in vivo relevance and predictive value of MPSs can be properly assessed as fit-for-purpose in specific applications, such as the assessment of drug toxicity, the identification of therapeutics or the understanding of human physiology or disease. Specifically, we distinguish designed features, which can be controlled via the design of the MPS, from emergent features, which describe cellular function, and propose methods for improving MPSs with readouts and sensors for the quantitative monitoring of complex physiology towards enabling wider end-user adoption and regulatory acceptance.

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Fig. 1: MPSs can control and monitor physiological features.
Fig. 2: Design principles of MPSs of the human vasculature.
Fig. 3: Design principles of MPSs of the human intestine.
Fig. 4: Design principles of MPSs of the human heart.
Fig. 5: Design principles of MPSs of the human brain.
Fig. 6: Technical advances for the quantification of designed physiological features in MPSs.
Fig. 7: Technical advances for the quantification of emergent physiological features in MPSs.

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Acknowledgements

This work was supported by the Netherlands Organ-on-Chip Initiative (an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture and Science of the Government of the Netherlands) and a Novo Nordisk Foundation grant (NNF21CC0073729; reNEW) (the latter to C.L.M.). We thank A. van den Berg, H. Clevers, P. M. Sarro, M. D. Ferrari, C. Wijmenga, S. A. Kushner, A. M. J. M. van den Maagdenberg and J. Gribnau for leadership in the Netherlands Organ-on-Chip Initiative, constructive discussions and creating the collaborative environment that led to this article. We thank M. Zuurmond for the graphical design of Figs. 1–7.

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  1. These authors contributed equally: Dennis M. Nahon, Renée Moerkens.

Authors and Affiliations

  1. Leiden University Medical Center, Leiden, the Netherlands

    Dennis M. Nahon, Jeroen M. Stein, Jean-Philippe Frimat, Mees N. S. de Graaf, Michel Hu, Dhanesh G. Kasi, Laura M. Windt, Berend J. van Meer, Valeria V. Orlova & Christine L. Mummery

  2. University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    Renée Moerkens, Kieu T. T. Le, Joram Mooiweer, Jelle Slager & Sebo Withoff

  3. Delft University of Technology, Delft, the Netherlands

    Hande Aydogmus, Milica Dostanić, Paul Motreuil-Ragot, Nele Revyn & Massimo Mastrangeli

  4. Erasmus University Medical Center, Rotterdam, the Netherlands

    Bas Lendemeijer, Cristina Gontan, Eva Niggl & Femke M. S. de Vrij

  5. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, the Netherlands

    Adriana Martínez-Silgado, Sangho Lim, Cayetano Pleguezuelos-Manzano & Jens Puschhof

  6. University of Twente, Enschede, the Netherlands

    Lena S. Koch, Heleen H. T. Middelkamp, José M. Rivera-Arbelaez, Mariia Zakharova & Andries D. van der Meer

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Contributions

D.M.N., R.M. and C.L.M. coordinated the project. D.M.N., R.M., C.L.M., A.D.v.d.M. and B.J.v.M. conceptualized the manuscript. D.M.N., R.M., H.A., B.L., J.M.S. and M.M. wrote the manuscript. D.M.N., R.M., B.J.v.M., V.V.O., F.M.S.d.V., S.W., M.M., A.D.v.d.M. and C.L.M. reviewed and edited the manuscript. D.M.N., R.M., H.A., B.L., J.M.S. and A.M.-S. conceptualized the figures. A.M.-S. designed the figures. D.M.N., R.M., H.A., B.L., A.M.-S., J.M.S., M.D., J.-P.F., C.G., M.N.S.d.G., M.H., D.G.K., L.S.K., K.T.T.L., S.L., H.H.T.M., J.M., P.M.-R., E.N., C.P.-M., J.P., N.R., J.M.R.-A., J.S., L.M.W., M.Z. and B.J.v.M. performed the literature research and participated in the process of selecting which literature to include.

Corresponding author

Correspondence to Christine L. Mummery.

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Competing interests

C.L.M. is a co-founder of Ncardia and an advisor to HeartBeat.bio and Sartorius. The other authors declare no competing interests.

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Nature Biomedical Engineering thanks Wilbur Lam, Milica Radisic, Gordana Vunjak-Novakovic and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Nahon, D.M., Moerkens, R., Aydogmus, H. et al. Standardizing designed and emergent quantitative features in microphysiological systems. Nat. Biomed. Eng 8, 941–962 (2024). https://doi.org/10.1038/s41551-024-01236-0

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