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人类干细胞生物学中的嵌合动物模型。

Chimeric animal models in human stem cell biology.

作者信息

Glover Joel C, Boulland Jean-Luc, Halasi Gabor, Kasumacic Nedim

机构信息

Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Blindern 0317 Oslo, Norway.

出版信息

ILAR J. 2009;51(1):62-73. doi: 10.1093/ilar.51.1.62.

DOI:10.1093/ilar.51.1.62
PMID:20075498
Abstract

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

摘要

干细胞在再生医学中的临床应用严重依赖于动物模型的临床前研究。在本综述中,我们探讨了使用动物模型研究人类干细胞生物学的一些关键问题和挑战——实验标准化、体型、免疫屏障、细胞存活因子、宿主细胞与供体细胞融合以及体内成像和追踪。我们特别关注可用于在活体动物中追踪细胞的各种成像方式,比较它们的优缺点,并描述可能为体内动态评估干细胞行为带来新机会的技术发展。然后,我们概述了一些最常用的动物模型、它们的优缺点以及它们用于人类干细胞异种移植的示例,并分别综述了涉及啮齿动物、有蹄类动物、非人灵长类动物和鸡胚的模型。随着人类体细胞、胚胎和诱导多能干细胞使用的增加,这些动物模型的应用范围也将扩大。通过基因操作、细胞递送和体内成像方面的进展,可能会开发出越来越复杂的人类/动物嵌合模型用途。

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