Modeling normal and malignant human hematopoiesis in vivo through newborn NSG xenotransplantation

Modeling normal and malignant human hematopoiesis in vivo through newborn NSG xenotransplantation
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DOI:
10.1007/s12185-013-1467-9
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发表时间:
2013-12-01
影响因子:
2.1
通讯作者:
Ishikawa, Fumihiko
Ishikawa, Fumihiko
中科院分区:
医学4区
文献类型:
--
作者:
Ishikawa, Fumihiko

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已经开发了各种免疫受损小鼠品系来研究体内的人类正常和恶性干细胞。携带Il 2 rg的完全无效突变的NOD/SCID小鼠(NSG小鼠)缺乏T细胞、B细胞和NK细胞,并且支持人脐带血造血干细胞(CB HSC)和急性髓性白血病干细胞(AML LSC)的高水平植入。除了实现高水平的人造血细胞植入之外,使用新生NSG小鼠作为受体已经能够研究人CB HSC如何在体内产生成熟的免疫亚群。此外,通过将人LSC异种移植到新生NSG小鼠中来建立人原发性AML的体内模型,可以在体内检查人AML的功能特性,例如细胞周期、位置和自我更新能力。新生儿NSG异种移植模型的建立将有助于了解人类正常和恶性造血过程,并有助于开发新的血液病治疗方法。
Various strains of immune-compromised mice have been developed to investigate human normal and malignant stem cells in vivo. NOD/SCID mice harboring complete null mutation of Il2rg (NSG mice) lack T cells, B cells, and NK cells, and support high levels of engraftment by human cord blood hematopoietic stem cells (CB HSCs) and acute myeloid leukemia stem cells (AML LSCs). In addition to achieving high levels of human hematopoietic cell engraftment, use of newborn NSG mice as recipients has enabled the investigation into how human CB HSCs generate mature immune subsets in vivo. Moreover, through establishing an in vivo model of human primary AML by xeno-transplantation of human LSCs into newborn NSG mice, functional properties of human AML such as cell cycle, location, and self-renewal capacity can be examined in vivo. Newborn NSG xenogeneic transplantation model may facilitate the understanding of human normal and malignant hematopoiesis and contribute to the development of novel therapies against hematologic diseases.