実験動物応用研究部

ヒト疾患モデル研究室

医学生物学研究に使用される生体モデルは、マウスやラットなどのげっ歯類が汎用されており、飼育の簡便さやハンドリングのしやすさなどから実験動物のゴールデンスタンダードとなっています。 しかしながら、これらげっ歯類とヒトとではDNA配列の相違に基づいた分子機能が異なるために、ヒトへの十分な外挿性を持ったモデル動物の構築は困難でありました。

ヒト疾患モデル研究室では、ヒト造血幹細胞や末梢血単核球を免疫不全マウスに移入したヒト免疫系、造血系再構築マウスを作製し、アレルギー、新興・再興感染症、自己免疫疾患、GVHD(移植片対宿主病)などの疾患を再現したヒト化マウスを開発しています。 これらヒト化マウスモデルを用い、疾患のメカニズムを解明するための基礎研究をはじめ、創薬における薬効評価や安全性の前臨床試験が可能となる新しいスタンダードモデルの確立を目指しています。

ヒト疾患モデル研究室画像
※代表的な研究論文
  1. Chemically defined cytokine-free expansion of human haematopoietic stem cells.
    Sakurai M, Ishitsuka K, Ito R, Wilkinson AC, Kimura T, Mizutani E, Nishikii H, Sudo K, Becker HJ, Takemoto H, Sano T, Kataoka K, Takahashi S, Nakamura Y, Kent DG, Iwama A, Chiba S, Okamoto S, Nakauchi H, Yamazaki S.
    Nature. 2023 Mar 615(7950):127-133.
  2. Efficient differentiation of human neutrophils with recapitulation of emergency granulopoiesis in human G-CSF knockin humanized mice.
    Ito R, Katano I, Kwok IWH, Ng LG, Ida-Tanaka M, Ohno Y, Mu Y, Morita H, Nishinaka E, Nishime C, Mochizuki M, Kawai K, Chien TH, Yunqian Z, Yiping F, Hua LH, Celhar T, Yen Chan JK, Takahashi T, Goto M, Ogura T, Takahashi R, Ito M.
    Cell Rep. 2022 Dec 20;41(12):111841.
  3. HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice.
    Ohno Y, Ohshima S, Miyamoto A, Kametani F, Ito R, Tsuda B, Kasama Y, Nakada S, Kashiwagi H, Seki T, Yasuda A, Ando K, Ito M, Tokuda Y, Kametani Y.
    Sci Rep. 2021 Jun 17;11(1):12798.
  4. Bovine β-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/hGM-CSF transgenic mice.
    Ito R, Katano I, Otsuka I, Takahashi T, Suemizu H, Ito M, Simons PJ.
    Int Immunol. 2021 Mar 1;33(3):183-189.
  5. Exacerbation of pathogenic Th17-cell-mediated cutaneous graft-versus-host-disease in human IL-1β and IL-23 transgenic humanized mice.
    Ito R, Katano I, Otsuka I, Hanazawa A, Takahashi T, Kawai K, Yagoto M, Goto M, Ogura T, Takahashi R, Ito M.
    Biochem Biophys Res Commun. 2019 Aug 20;516(2): 480-485.
  6. Recent Advances in Allergy Research Using Humanized Mice.
    Ito R, Maruoka S, Gon Y, Katano I, Takahashi T, Ito M, Izuhara K, Nunomura S.
    Int J Mol Sci. 2019 Jun 4;20(11):2740.
  7. A humanized mouse model to study asthmatic airway inflammation via the human IL-33/IL-13 axis.
    Ito R, Maruoka S, Soda K, Katano I, Kawai K, Yagoto M, Hanazawa A, Takahashi T, Ogura T, Goto M, Takahashi R, Toyoshima S, Okayama Y, Izuhara K, Gon Y, Hashimoto S, Ito M, Nunomura S.
    JCI Insight. 2018 Nov 2;3(21).
  8. Humanized mouse models: Application to human diseases.
    Ito R, Takahashi T, Ito M.
    J Cell Physiol. 2018 May;233(5):3723-3728.
  9. A novel in vivo model for predicting myelotoxicity of chemotherapeutic agents using IL-3/GM-CSF transgenic humanized mice.
    Ito R, Nagai D, Igo N, Okuda Y, Sekine K, Ichimura E, Katano I, Mizushima T, Goto M, Ohnishi Y, Ito M, Okamoto K.
    Toxicology Letter. 2017 Nov 5;281:152-157.
  10. A Novel Xenogeneic Graft-Versus-Host Disease Model for Investigating the Pathological Role of Human CD4+ or CD8+ T Cells Using Immunodeficient NOG Mice.
    Ito R, Katano I, Kawai K, Yagoto M, Takahashi T, Ka Y, Ogura T, Takahashi R, Ito M.
    Am J Transplant. 2017 May;17(5):1216-1228.
  11. Establishment of a human allergy model using human IL-3/GM-CSF transgenic NOG mice.
    Ito R, Takahashi T, Katano I, Kawai K, Kamisako T, Ogura T, Ida-Tanaka M, Suemizu H, Nunomura S, Ra C, Mori A, Aiso S, Ito M.
    Journal of Immunology. 2013 Sep 15;191:2890-2899.
  12. Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rγnull mice is attributed to a lack of CD11c+B220+CD122+ cells.
    Ito R, Katano I, Ida-Tanaka M, Kamisako T, Kawai K, Suemizu H, Aiso S, Ito M.
    Journal of Immunology. 2012 Nov 1;189(9):4313-4320.
  13. Osteosclerosis and inhibition of human hematopoiesis in NOG mice expressing human Delta-like 1 in osteoblasts.
    Ito R, Negishi N, Irie N, Matsuo K, Suzuki D, Katano I, Hayakawa E, Kawai K, Kamisako T, Ogura T, Hozumi K, Ando K, Aiso S, Tamaoki N, Habu S, Ito M.
    Exp Hematol. 2012 Nov;40(11):953-963.e3.
  14. Current advances in humanized mouse models.
    Ito R, Takahashi T, Katano I, Ito M.
    Cellular and Molecular Immunology. 2012 May;9(3):208-214.
  15. Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice.
    Ito R, Katano I, Kawai K, Hirata H, Ogura T, Kamisako T, Eto T, Ito M.
    Transplantation. 2009 Jun;87(11):1654–1658.
  16. Antigen-specific antibody production of human B cells in NOG mice reconstituted with the human immune system.
    Ito R, Shiina M, Saito Y, Tokuda Y, Kametani Y, Habu S.
    Curr Top Microbiol Immunol. 2008;324:95-107.

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