報告書番号

V09011

タイトル（和文）

ヒト化マウスを用いた新規ヒト健康リスク評価システムの開発 －ヒト化マウスの作製とその評価－

タイトル（英文）

Development of novel system for assessment of human health using humanized mice - Establishment and evaluation of humanized mice -

概要 （図表や脚注は「報告書全文」に掲載しております）

本報告では、ヒト化マウスのヒト健康リスク評価システムへの応用に向け、ヒト化マウス内での各種ヒト血球細胞の分化、成熟過程を評価し、構築された造血、免疫系のヒトとの類似性を検討した。X線照射により骨髄を破壊した重度免疫不全マウス（NOGマウス）に対し、尾静脈よりヒト臍帯血由来造血幹細胞を移植することでヒト化マウスを作製した。ヒト化マウスより採取した骨髄中に含まれた細胞種を解析した結果、尾静脈より移植したヒト造血幹細胞はマウスの骨髄に移入、定着したと考えられた。更に、骨髄、胸腺、脾臓、血液に含まれた細胞種を総合的に解析した結果、マウス骨髄に定着したヒト造血幹細胞はその後多種の血球細胞に分化したことが確認された。また、それら分化細胞はヒト体内での細胞成熟過程と同様の経路を経て成熟していることが示唆された。以上より、ヒト化マウス内にはヒトと類似した造血系、免疫系が構築されていると考えられ、血液毒性、免疫毒性を対象としたヒト健康リスク評価システムへ応用可能であると考えられた。

概要 （英文）

There are various risk factors, which influence to human health, in living environment, and it has been desired to assess the factors exactly and to manage those properly. However, the present system to assess the factors is not able to assess fully the risks under consideration of species-differences between human and experimental animals. Recently, humanized mice are paid attentions as a useful in vivo system that mimic human. Herein, we evaluated the process of maturation and differentiation of hematopoietic cells in humanized mouse to utilize humanized mice as a novel system for risk assessment of human health. Humanized mice were established by transplanting human CD34+ cord blood cells into irradiated severely immunodeficient NOD/Shi-scid-IL2Rgnull mice, and the phenotypes of blood cells contained in bone marrow, thymus, spleen and peripheral blood from the humanized mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted hematopoietic stem cells through the tail vein were homed and fixed to bone marrow and the cells differentiated to various blood cells and migrated to the other organs. About 100% of blood cells in thymus were human cells. Furthermore, profiles of contained blood cell in each organ suggested that each differentiated blood cells were matured through specific process/organs which is the same as that in human body. Thus, it was considered that human hematopoietic and immune system were introduced in humanized mice and the humanized mice were useful to the system for risk assessment of human health.

報告者

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