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Overcoming immunological barriers in regenerative medicine

Nature Biotechnology volume 32, pages 786–794 (2014)Cite this article

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Abstract

Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists.

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Figure 1: The likelihood of encountering immunological barriers depends on the type of cells and tissues used in regenerative therapies.
Figure 2: Molecular basis of T cell allorecognition and activation.

Kim Caesar/Nature Publishing Group

Figure 3: Antigen-specific tolerance induction by apoptotic, polymeric or protein carriers.

Kim Caesar/Nature Publishing Group

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Acknowledgements

We thank A.Z. Tuckett for valuable feedback and her input in the design of Figure 3.

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Authors and Affiliations

  1. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Johannes L Zakrzewski

  2. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Marcel R M van den Brink

  3. Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Marcel R M van den Brink

  4. Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Jeffrey A Hubbell

  5. Institute for Molecular Engineering, University of Chicago, Chicago, Illinois, USA

    Jeffrey A Hubbell

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  1. Johannes L Zakrzewski
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  2. Marcel R M van den Brink
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  3. Jeffrey A Hubbell
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Correspondence to Johannes L Zakrzewski.

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Competing interests

Jeffrey Hubbell wishes to declare that he is founder and shareholder of Anokion SA, which is commercializing the technology described in the manuscript regarding binding antigens to erythrocytes for tolerization.

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Zakrzewski, J., van den Brink, M. & Hubbell, J. Overcoming immunological barriers in regenerative medicine. Nat Biotechnol 32, 786–794 (2014). https://doi.org/10.1038/nbt.2960

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