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  • Review Article
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Bioengineering translational models of lymphoid tissues

Nature Reviews Bioengineering volume 1, pages 731–748 (2023)Cite this article

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Abstract

Bioengineered models of human tissues have the potential to revolutionize human health by providing a translational platform to investigate disease mechanisms and develop new therapies. Recreating human immune biology is challenging owing to its unique complexity and diversity at the molecular, cellular, tissue and system levels. Advances in immunotherapy have contributed to the emergence of immuno-engineering as a new discipline that applies engineering principles to modulate and emulate the immune system. In synergy with single-cell sequencing, spatial omics, systems immunology, organoids and organ-on-a-chip technologies, these are helping to decipher and recreate human immune components and responses in vitro at a high level of biological fidelity. In this Review, we contextualize the needs for predictive non-clinical models of human immune responses and we overview recent advances in bioengineering models of lymphoid tissues and immune-competent non-lymphoid tissues. We focus on models of the thymus, lymph nodes and intestinal mucosa as examples requiring different degrees of biological and technical complexity. We highlight the experimental demonstrations of their translational value and propose avenues to boost their impact as non-clinical models for immunotherapies.

Key points

  • Preclinical studies for immunotherapies do not translate well into clinical outcomes, in part because animals or simplistic in vitro models do not sufficiently recreate complex human immune responses.

  • High-resolution spatial omics and single-cell immune repertoire sequencing can fill important knowledge gaps and guide engineering principles of the human immune system, in particular deciphering and recreating T cell and B cell diversity.

  • Recent advances in bioengineered models of lymphoid tissues, such as the thymus and lymphoid follicles, and mimicry of resident immunity in various tissue models demonstrate the possibility to recreate innate and adaptive immune responses in vitro and in vivo.

  • The translational value of models of the immune system for applications in drug research and development could be enhanced by incorporating benchmarks and readouts relevant to preclinical and clinical contexts.

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Fig. 1: Immune cell types, blood and lymphoid tissues.
Fig. 2: Building bioengineered lymphoid models that recapitulate primary tissue structure and function.
Fig. 3: Connecting bioengineered models of lymphoid tissues and intestinal immunity.

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Acknowledgements

We thank D. Mooney, A. Khalil, B. Lowe, A. Singh and Z. Zhong for providing unpublished immunofluorescence images of thymus and tonsil primary tissues and organoids (Fig. 2). Y.S.M. acknowledges support from the CancerCare Manitoba Foundation.

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Authors and Affiliations

  1. School of Biomedical Engineering, University of British Columbia, Vancouver, Canada

    Yale S. Michaels

  2. CancerCare Manitoba Research Institute, Winnipeg, Canada

    Yale S. Michaels

  3. Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada

    Yale S. Michaels

  4. Human Organs, Physiology and Engineering (HOPE), Wellcome Leap, Los Angeles, CA, USA

    Cara F. Buchanan & Annie Moisan

  5. Institute of Human Biology, Roche Innovation Center, Basel, Switzerland

    Nikolche Gjorevski

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A.M. and N.G. conceptualized the manuscript. A.M., N.G., C.F.B. and Y.S.M. wrote the manuscript. A.M. and Y.S.M. edited the manuscript.

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Michaels, Y.S., Buchanan, C.F., Gjorevski, N. et al. Bioengineering translational models of lymphoid tissues. Nat Rev Bioeng 1, 731–748 (2023). https://doi.org/10.1038/s44222-023-00101-0

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