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人源化小鼠中人造血细胞来源白细胞谱系的综合评估。

Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

机构信息

Environmental Risk Assessment Sector, Environmental Science Research Laboratory, Central Research Institute of Electric Power Industry, 1646 Abiko, Abiko-City, Chiba 270-1194, Japan.

出版信息

J Biosci Bioeng. 2012 Apr;113(4):529-35. doi: 10.1016/j.jbiosc.2011.11.011. Epub 2011 Dec 13.

DOI:10.1016/j.jbiosc.2011.11.011
PMID:22169092
Abstract

Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice.

摘要

最近,人们利用经过基因或细胞生物工程改造的动物部分,来克服种间差异,创造出了“人性化动物”。在此,我们分析了各种人源化小鼠中不同人类白细胞亚群的分化状态细节,并全面评估了人源化小鼠与人类之间白细胞谱系的相似性。我们通过将人 CD34(+)脐血细胞移植到辐射严重免疫缺陷的 NOD/Shi-scid/IL2Rγ(null)(NOG)小鼠中,建立了人源化小鼠模型,并在细胞移植后每月分析一次直到 4 个月,以分析来自小鼠骨髓、胸腺、脾脏和外周血的人细胞的表型。分析结果表明,通过尾静脉移植的人造血干细胞成功归巢并植入了小鼠骨髓。随后,分化的白细胞迁移到各种组织中。胸腺中的几乎所有白细胞都是人细胞。此外,对各种组织和器官中人类白细胞分化状态的分析表明,在小鼠中很可能会发展出类似人类的白细胞谱系。

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