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Designing natural and synthetic immune tissues

Nature Materials volume 17, pages 484–498 (2018)Cite this article

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Abstract

Vaccines and immunotherapies have provided enormous improvements for public health, but there are fundamental disconnects between where most studies are performed—in cell culture and animal models—and the ultimate application in humans. Engineering immune tissues and organs, such as bone marrow, thymus, lymph nodes and spleen, could be instrumental in overcoming these hurdles. Fundamentally, designed immune tissues could serve as in vitro tools to more accurately study human immune function and disease, while immune tissues engineered for implantation as next-generation vaccines or immunotherapies could enable direct, on-demand control over generation and regulation of immune function. In this Review, we discuss recent interdisciplinary strategies that are merging materials science and immunology to create engineered immune tissues in vitro and in vivo. We also highlight the hurdles facing these approaches and the need for comparison to existing clinical options, relevant animal models, and other emerging technologies.

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Fig. 1: Immune tissues play distinct roles in immune cell development.
Fig. 2: Immune organoids allow for the development of germinal-centre-like B cells that undergo complex immunological processes.
Fig. 3: Engineered bone marrow on-a-chip replicates function of bone marrow in vivo.
Fig. 4: Engineered scaffolds recruit APCs to access tumour antigen and improve function after migration to LNs.
Fig. 5: Local changes in lymph node structure from direct injection of tolerogenic microparticles into the lymph nodes of mice with autoimmune disease drive systemic changes in immune signalling.
Fig. 6: Engineering immune tissues can restore immune functions in vivo.
Fig. 7: New immunological insight informs immune tissue engineering design.

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Acknowledgements

This work was supported in part by the United States Department of Veterans Affairs grant no. 1I01BX003690, NIH grant no. R01EB026896, NSF CAREER grant no. 1351688, the National Multiple Sclerosis Society grant no. RG-1501-02968, NIH grant no. 1R01AI062765, NIH grant no. 1R01AI114496, the Damon Runyon Foundation grant no. DRR3415, and Juvenile Diabetes Research Foundation grant no. 2-SRA-2016-319-S-B. H.B.E. is a trainee of the NIH T32 Training Program in Cell and Molecular Biology (T32GM080201). C.M.J. is a young investigator of the Alliance for Cancer Gene Therapy (grant no. 15051543) and the Melanoma Research Alliance (grant no. 348963).

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Authors and Affiliations

  1. Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA

    Emily A. Gosselin, Haleigh B. Eppler & Christopher M. Jewell

  2. Molecular and Cellular Biology, Biological Sciences Training Program, University of Maryland, College Park, MD, USA

    Haleigh B. Eppler & Christopher M. Jewell

  3. Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Jonathan S. Bromberg

  4. Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA

    Jonathan S. Bromberg

  5. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

    Jonathan S. Bromberg & Christopher M. Jewell

  6. Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, USA

    Jonathan S. Bromberg & Christopher M. Jewell

  7. Robert E. Fischell Institute for Biomedical Devices, College Park, MD, USA

    Christopher M. Jewell

  8. United States Department of Veterans Affairs, Maryland VA Health Care System, Baltimore, MD, USA

    Christopher M. Jewell

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Gosselin, E.A., Eppler, H.B., Bromberg, J.S. et al. Designing natural and synthetic immune tissues. Nature Mater 17, 484–498 (2018). https://doi.org/10.1038/s41563-018-0077-6

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