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

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 l...

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Autores principales: Itoh, Manabu, Mukae, Yosuke, Kitsuka, Takahiro, Arai, Kenichi, Nakamura, Anna, Uchihashi, Kazuyoshi, Toda, Shuji, Matsubayashi, Kumika, Oyama, Jun-ichi, Node, Koichi, Kami, Daisuke, Gojo, Satoshi, Morita, Shigeki, Nishida, Takahiro, Nakayama, Koichi, Kobayashi, Eiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529409/
https://www.ncbi.nlm.nih.gov/pubmed/31113942
http://dx.doi.org/10.1038/s41467-019-10107-1
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author Itoh, Manabu
Mukae, Yosuke
Kitsuka, Takahiro
Arai, Kenichi
Nakamura, Anna
Uchihashi, Kazuyoshi
Toda, Shuji
Matsubayashi, Kumika
Oyama, Jun-ichi
Node, Koichi
Kami, Daisuke
Gojo, Satoshi
Morita, Shigeki
Nishida, Takahiro
Nakayama, Koichi
Kobayashi, Eiji
author_facet Itoh, Manabu
Mukae, Yosuke
Kitsuka, Takahiro
Arai, Kenichi
Nakamura, Anna
Uchihashi, Kazuyoshi
Toda, Shuji
Matsubayashi, Kumika
Oyama, Jun-ichi
Node, Koichi
Kami, Daisuke
Gojo, Satoshi
Morita, Shigeki
Nishida, Takahiro
Nakayama, Koichi
Kobayashi, Eiji
author_sort Itoh, Manabu
collection PubMed
description 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.
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spelling pubmed-65294092019-05-23 Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes Itoh, Manabu Mukae, Yosuke Kitsuka, Takahiro Arai, Kenichi Nakamura, Anna Uchihashi, Kazuyoshi Toda, Shuji Matsubayashi, Kumika Oyama, Jun-ichi Node, Koichi Kami, Daisuke Gojo, Satoshi Morita, Shigeki Nishida, Takahiro Nakayama, Koichi Kobayashi, Eiji Nat Commun Article 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. Nature Publishing Group UK 2019-05-21 /pmc/articles/PMC6529409/ /pubmed/31113942 http://dx.doi.org/10.1038/s41467-019-10107-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Itoh, Manabu
Mukae, Yosuke
Kitsuka, Takahiro
Arai, Kenichi
Nakamura, Anna
Uchihashi, Kazuyoshi
Toda, Shuji
Matsubayashi, Kumika
Oyama, Jun-ichi
Node, Koichi
Kami, Daisuke
Gojo, Satoshi
Morita, Shigeki
Nishida, Takahiro
Nakayama, Koichi
Kobayashi, Eiji
Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
title Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
title_full Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
title_fullStr Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
title_full_unstemmed Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
title_short Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
title_sort development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529409/
https://www.ncbi.nlm.nih.gov/pubmed/31113942
http://dx.doi.org/10.1038/s41467-019-10107-1
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