Reproductive Biology and Endocrinology Open Access Derivation and Characterization of Monkey Embryonic Stem Cells
Reproductive Biology and Endocrinology Open Access Derivation and Characterization of Monkey Embryonic Stem Cells
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K-Y Francis Pau;D. Wolf;K-Y Francis Email;P. Edu ; Don;Wolf
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作者：
K-Y Francis Pau;D. Wolf;K-Y Francis Email;P. Edu ; Don;Wolf
基于胚胎干细胞的治疗在神经退行性疾病的治疗中具有巨大的潜力。然而，在实现临床应用之前，必须在动物模型中建立这种治疗方法的安全性、有效性和可行性。恒河猴在生理学和遗传学上与人类相似，因此是生物医学研究的临床相关动物模型，特别是专注于神经退行性疾病的研究。未分化的猴ES细胞可以维持在多能性状态下多次传代，其特征在于代表胚胎细胞表面分子、酶和转录因子的标记物的集合库。它们也可以通过表观遗传方案分化成所有三个胚胎胚层的谱系特异性表型。然而，对于基于细胞的治疗，在ES细胞增殖和分化的过程中必须确保ES细胞及其后代的质量。虽然只研究了有限数量的灵长类动物ES细胞系，但很可能存在大量的系间变异性。这意味着不同的ES细胞系可能在发育阶段、谱系定型、核型正常性、基因表达或分化潜能方面存在差异。这些变量，遗传和/或诱导表观遗传，进行明显的并发症的治疗应用。本实验室从体外培养的囊胚中分离并鉴定了恒河猴ES细胞系。所有测试的细胞系都具有形成多能拟胚体和巢蛋白阳性祖细胞的潜力。这些ES细胞后代可以分化成代表内胚层、中胚层和外胚层谱系的表型。这篇综述文章介绍了猴ES细胞系的来源，未分化表型的特征，以及它们分化成谱系特异性的，特别是神经的表型。灵长类动物ES细胞为基础的治疗的承诺和局限性也进行了讨论。胚胎干细胞（Embryonic stem cells，ES）是由Martin [1]和Evans和考夫曼[2]于1981年首次从近交系小鼠胚胎的内细胞团（inner cell mass，ICM）中分离获得的。最近，ES细胞成功地来源于非人灵长类动物和人类胚胎[3 - 5]。美国国立卫生研究院在2001年列出了64种可用于研究的人类ES细胞系[6];然而，只有少数被表征和研究。同样，除了建立多能性和遗传稳定性外，20多种猴ES细胞系中只有不到7种得到了充分表征[3，4，7 - 9]。即使在小鼠中，大多数ES细胞研究也是用单一近交系小鼠细胞系（品系129）进行的。灵长类ES细胞系之间的多样性程度目前尚不清楚。文章：.
Embryonic stem (ES) cell based therapy carries great potential in the treatment of neurodegenerative diseases. However, before clinical application is realized, the safety, efficacy and feasibility of this therapeutic approach must be established in animal models. The rhesus macaque is physiologically and phylogenetically similar to the human, and therefore, is a clinically relevant animal model for biomedical research, especially that focused on neurodegenerative conditions. Undifferentiated monkey ES cells can be maintained in a pluripotent state for many passages, as characterized by a collective repertoire of markers representing embryonic cell surface molecules, enzymes and transcriptional factors. They can also be differentiated into lineage-specific phenotypes of all three embryonic germ layers by epigenetic protocols. For cell-based therapy, however, the quality of ES cells and their progeny must be ensured during the process of ES cell propagation and differentiation. While only a limited number of primate ES cell lines have been studied, it is likely that substantial inter-line variability exists. This implies that diverse ES cell lines may differ in developmental stages, lineage commitment, karyotypic normalcy, gene expression, or differentiation potential. These variables, inherited genetically and/or induced epigenetically, carry obvious complications to therapeutic applications. Our laboratory has characterized and isolated rhesus monkey ES cell lines from in vitro produced blastocysts. All tested cell lines carry the potential to form pluripotent embryoid bodies and nestin-positive progenitor cells. These ES cell progeny can be differentiated into phenotypes representing the endodermal, mesodermal and ectodermal lineages. This review article describes the derivation of monkey ES cell lines, characterization of the undifferentiated phenotype, and their differentiation into lineage-specific, particularly neural, phenotypes. The promises and limitations of primate ES cell-based therapy are also discussed. Review Embryonic stem (ES) cells were first derived from the inner cell mass (ICM) of inbred mouse embryos in 1981 by Martin [1] and Evans and Kaufman [2]. Recently, ES cells were successfully derived from non-human primate and human embryos [3-5]. The National Institutes of Health listed 64 human ES cell lines available for research in 2001 [6]; however, only a few had been characterized and studied. Similarly, less than 7 of the more than 20 monkey ES cell lines have been well characterized apart from establishing pluripotency and genetic stability [3,4,7-9]. Even in the mouse, most ES cell studies have been performed with a single inbred mouse cell line (strain 129). The extent of diversity among primate ES cell lines is currently unknown. article: …