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Generation of a synthetic lymphoid tissue–like organoid in mice

Nature Biotechnology volume 22, pages 15391545 (2004) | Download Citation

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Abstract

Stromal cells play an important role in the formation of the normal organized microarchitecture of secondary lymphoid organs. Here we demonstrate that a tissue-engineered, lymphoid tissue–like organoid, which was constructed by transplantation of stromal cells embedded in biocompatible scaffolds into the renal subcapsular space in mice, had an organized tissue structure similar to secondary lymphoid organs. This organoid contained compartmentalized B-cell and T-cell clusters, high endothelial venule-like vessels, germinal centers and follicular dendritic cell networks. Furthermore, the organoid was transplantable to naive normal or severe combined immunodeficiency (SCID) mice, and antigen-specific, IgG-isotype antibody formation could be induced soon after intravenous administration of the antigen. This simplified system of lymphoid tissue–like organoid construction will facilitate analyses of cell-cell interactions required for development of secondary lymphoid organs and efficient induction of adaptive immune responses, and may have possible applications in the treatment of immune deficiency.

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Acknowledgements

We thank Takehisa Matsuda for fruitful discussions and biocompatible materials, Peter Burrows for critical reading and suggestions. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology in Japan.

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  1. Research Unit for Immune Surveillance, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.

    • Sachiko Suematsu
    •  & Takeshi Watanabe

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The authors declare no competing financial interests.

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Correspondence to Sachiko Suematsu.

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DOI

https://doi.org/10.1038/nbt1039

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