Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes

Manabu Itoh; Yosuke Mukae; Takahiro Kitsuka; Kenichi Arai; Anna Nakamura; Kazuyoshi Uchihashi; Shuji Toda; Kumika Matsubayashi; Jun ichi Oyama; Koichi Node; Daisuke Kami; Satoshi Gojo; Shigeki Morita; Takahiro Nishida; Koichi Nakayama; Eiji Kobayashi

doi:10.1038/s41467-019-10107-1

Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes

Manabu Itoh, Yosuke Mukae, Takahiro Kitsuka, Kenichi Arai, Anna Nakamura, Kazuyoshi Uchihashi, Shuji Toda, Kumika Matsubayashi, Jun ichi Oyama, Koichi Node, Daisuke Kami, Satoshi Gojo, Shigeki Morita, Takahiro Nishida, Koichi Nakayama^*, Eiji Kobayashi

^*Corresponding author for this work

Department of Clinical Biomaterial Applied Science

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Before they are used in the clinical setting, the effectiveness of artificially produced human-derived tissue-engineered medical products should be verified in an immunodeficient animal model, such as severe combined immunodeficient mice. However, small animal models are not sufficient to evaluate large-sized products for human use. Thus, an immunodeficient large animal model is necessary in order to properly evaluate the clinical efficacy of human-derived tissue-engineered products, such as artificial grafts. Here we report the development of an immunodeficient pig model, the operational immunodeficient pig (OIDP), by surgically removing the thymus and spleen, and creating a controlled immunosuppressive protocol using a combination of drugs commonly used in the clinical setting. We find that this model allows the long-term accommodation of artificial human vascular grafts. The development of the OIDP is an essential step towards a comprehensive and clinically relevant evaluation of human cell regeneration strategies at the preclinical stage.

Original language	English
Article number	2244
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10107-1
State	Published - 2019/12/01

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Itoh, M., Mukae, Y., Kitsuka, T., Arai, K., Nakamura, A., Uchihashi, K., Toda, S., Matsubayashi, K., Oyama, J. I., Node, K., Kami, D., Gojo, S., Morita, S., Nishida, T., Nakayama, K., & Kobayashi, E. (2019). Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes. Nature Communications, 10(1), Article 2244. https://doi.org/10.1038/s41467-019-10107-1

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title = "Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes",

abstract = "Before they are used in the clinical setting, the effectiveness of artificially produced human-derived tissue-engineered medical products should be verified in an immunodeficient animal model, such as severe combined immunodeficient mice. However, small animal models are not sufficient to evaluate large-sized products for human use. Thus, an immunodeficient large animal model is necessary in order to properly evaluate the clinical efficacy of human-derived tissue-engineered products, such as artificial grafts. Here we report the development of an immunodeficient pig model, the operational immunodeficient pig (OIDP), by surgically removing the thymus and spleen, and creating a controlled immunosuppressive protocol using a combination of drugs commonly used in the clinical setting. We find that this model allows the long-term accommodation of artificial human vascular grafts. The development of the OIDP is an essential step towards a comprehensive and clinically relevant evaluation of human cell regeneration strategies at the preclinical stage.",

author = "Manabu Itoh and Yosuke Mukae and Takahiro Kitsuka and Kenichi Arai and Anna Nakamura and Kazuyoshi Uchihashi and Shuji Toda and Kumika Matsubayashi and Oyama, {Jun ichi} and Koichi Node and Daisuke Kami and Satoshi Gojo and Shigeki Morita and Takahiro Nishida and Koichi Nakayama and Eiji Kobayashi",

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Itoh, M, Mukae, Y, Kitsuka, T, Arai, K, Nakamura, A, Uchihashi, K, Toda, S, Matsubayashi, K, Oyama, JI, Node, K, Kami, D, Gojo, S, Morita, S, Nishida, T, Nakayama, K & Kobayashi, E 2019, 'Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes', Nature Communications, vol. 10, no. 1, 2244. https://doi.org/10.1038/s41467-019-10107-1

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AU - Itoh, Manabu

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AU - Kitsuka, Takahiro

AU - Arai, Kenichi

AU - Nakamura, Anna

AU - Uchihashi, Kazuyoshi

AU - Toda, Shuji

AU - Matsubayashi, Kumika

AU - Oyama, Jun ichi

AU - Node, Koichi

AU - Kami, Daisuke

AU - Gojo, Satoshi

AU - Morita, Shigeki

AU - Nishida, Takahiro

AU - Nakayama, Koichi

AU - Kobayashi, Eiji

PY - 2019/12/1

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Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes

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