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

开发可长期容纳人工血管的免疫缺陷猪模型

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作者: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 Kobayashi0

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.

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