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犬胚胎来源的干细胞与人类疾病模型

Canine embryo-derived stem cells and models for human diseases.

作者信息

Schneider Marlon R, Wolf Eckhard, Braun Joachim, Kolb Hans-Jochem, Adler Heiko

机构信息

Institut fuür Molekulare Tierzucht und Biotechnologie, Genzentrum der LMU München, München, Germany.

出版信息

Hum Mol Genet. 2008 Apr 15;17(R1):R42-7. doi: 10.1093/hmg/ddn078.

Abstract

Embryonic stem (ES) cells are pluripotent and permanent cell lines which can differentiate into cell types of all the three germ layers. These features imply multiple opportunities for clinical applications in tissue engineering and regenerative medicine. Most of our knowledge on the biology and technology of ES cells is derived from studies with mouse ES cells. While appropriate for proof-of-principle studies, the mouse model has limitations in its application in translational, pre-clinical studies. This is particularly true for studies evaluating the safety and efficacy of stem cell therapies. For this purpose, large animal models more closely mimicking important aspects of human anatomy, physiology and pathology than mouse models are urgently needed. In this context, the dog is an excellent candidate: the plethora of different dog breeds offer a large phenotypic and genetic variability, which can be exploited increasingly well due to the advanced status of the dog genome project and the rapidly growing box of genomic tools. Recently, the first pluripotent canine embryo-derived stem cells have been described, further increasing the potential of the dog as a model system for regenerative medicine. Although these cells express alkaline phosphatase, NANOG and OCT4, and can be differentiated in vitro towards endoderm-, mesoderm- and ectoderm-lineages (typical features of human and mouse ES cells), their in vivo differentiation capability, i.e. formation of teratomas in immunodeficient mice or contribution to chimeric animals, remains to be demonstrated. Here, we discuss the features of reported canine embryo-derived cells and their potential applications in basic and translational biomedical research.

摘要

胚胎干细胞(ES细胞)是多能性的永久性细胞系,能够分化为所有三个胚层的细胞类型。这些特性意味着在组织工程和再生医学的临床应用中有多种机会。我们对ES细胞生物学和技术的大部分了解都来自对小鼠ES细胞的研究。虽然适用于原理验证研究,但小鼠模型在转化性临床前研究中的应用存在局限性。对于评估干细胞疗法的安全性和有效性的研究尤其如此。为此,迫切需要比小鼠模型更能紧密模拟人体解剖学、生理学和病理学重要方面的大型动物模型。在这种背景下,狗是一个极佳的候选对象:大量不同的犬种提供了巨大的表型和遗传变异性,由于犬基因组计划的先进地位和快速增长的基因组工具库,这种变异性能够得到越来越充分的利用。最近,已经报道了首批多能性犬胚胎来源的干细胞,这进一步增加了狗作为再生医学模型系统的潜力。尽管这些细胞表达碱性磷酸酶、NANOG和OCT4,并且能够在体外向内胚层、中胚层和外胚层谱系分化(这是人和小鼠ES细胞的典型特征),但其体内分化能力,即在免疫缺陷小鼠中形成畸胎瘤或对嵌合体动物的贡献,仍有待证明。在这里,我们讨论已报道的犬胚胎来源细胞的特性及其在基础和转化性生物医学研究中的潜在应用。

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