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Engineering organoids

Nature Reviews Materials volume 6, pages 402–420 (2021)Cite this article

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Abstract

Organoids are in vitro miniaturized and simplified model systems of organs that have gained enormous interest for modelling tissue development and disease, and for personalized medicine, drug screening and cell therapy. Despite considerable success in culturing physiologically relevant organoids, challenges remain to achieve real-life applications. In particular, the high variability of self-organizing growth and restricted experimental and analytical access hamper the translatability of organoid systems. In this Review, we argue that many limitations of traditional organoid culture can be addressed by engineering approaches at all levels of organoid systems. We investigate cell surface and genetic engineering approaches, and discuss stem cell niche engineering based on the design of matrices that allow spatiotemporal control of organoid growth and shape-guided morphogenesis. We examine how microfluidic approaches and lessons learnt from organs-on-a-chip enable the integration of mechano-physiological parameters and increase accessibility of organoids to improve functional readouts. Applying engineering principles to organoids increases reproducibility and provides experimental control, which will, ultimately, be required to enable clinical translation.

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Fig. 1: Tissue-derived organoids.
Fig. 2: Pluripotent stem-cell-derived organoids.
Fig. 3: Engineering approaches for organoids.
Fig. 4: Engineering cells for guided morphogenesis.
Fig. 5: Engineering the niche.
Fig. 6: Systemic context engineering for organoid cultures.
Fig. 7: Microengineered platforms for live organoid monitoring.

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Acknowledgements

The authors thank Stefano Davide Vianello for preparing the illustrations and his much-valued contributions editing the text, and thank Bilge Sen Elci and Antonius Chrisnandy for discussions and comments on the manuscript. M.P.L.’s work in the area of organoid biology and technology is supported by the Swiss National Science Foundation (#310030_179447), École Polytechnique Fédérale de Lausanne (EPFL), the European Union’s Horizon 2020 research and innovation programme (INTENS, #668294), the Personalized Health and Related Technologies initiative from the ETH Board, the National Center of Competence in Research (NCCR) Bio-Inspired Materials, the FreeNovation funding program of the Novartis Research Foundation, the Marie Skłodowska-Curie European Training Network ‘EUROoC’ (H2020-MSCA-ITN-2018) and the Vienna Science and Technology Fund (WWTF). The authors apologize to all researchers and colleagues whose work could not be considered.

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Authors and Affiliations

  1. Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    Moritz Hofer & Matthias P. Lutolf

  2. Institute of Chemical Sciences and Engineering, School of Basic Science (SB), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    Matthias P. Lutolf

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  1. Moritz Hofer
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  2. Matthias P. Lutolf
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M.H. researched data for the article, made substantial contributions to discussions of the content and wrote the article. M.P.L. reviewed and edited the manuscript before submission.

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Correspondence to Matthias P. Lutolf.

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Hofer, M., Lutolf, M.P. Engineering organoids. Nat Rev Mater 6, 402–420 (2021). https://doi.org/10.1038/s41578-021-00279-y

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