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Nat Commun. 2019 May 21;10(1):2244. doi: 10.1038/s41467-019-10107-1.

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

Author information

1
Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine, Saga University, Saga, Japan.
2
Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Saga, Japan.
3
Department of Surgical Pathology, National Hospital Organization Saga Hospital, Saga, Japan.
4
Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
5
Cyfuse Biomedical K. K., Tokyo, Japan.
6
Department of Cardiovascular Medicine, Faculty of Medicine, Saga University, Saga, Japan.
7
Department of Regenerative Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
8
Department of Cardiovascular Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
9
Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Saga, Japan. nakayama@me.saga-u.ac.jp.
10
Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan. organfabri@a2.keio.jp.

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.

PMID:
31113942
PMCID:
PMC6529409
DOI:
10.1038/s41467-019-10107-1
[Indexed for MEDLINE]
Free PMC Article

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