Derivation and characterization of monkey embryonic stem cells.
Derivation and characterization of monkey embryonic stem cells.
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DOI：
10.1186/1477-7827-2-41
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发表时间：
2004-06-16
期刊：
影响因子：
--
通讯作者：
Wolf, Don P
中科院分区：
文献类型：
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作者：
Pau, K-Y Francis;Wolf, Don P
基于胚胎干（ES）细胞的疗法在治疗神经退行性疾病方面具有巨大潜力。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。恒河猴在生理和系统发育上与人类相似，因此是生物医学研究的临床相关动物模型，特别是针对神经退行性疾病的研究。未分化的猴 ES 细胞可以在多次传代中维持多能状态，其特征是代表胚胎细胞表面分子、酶和转录因子的一系列标记物。它们还可以通过表观遗传协议分化为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，ES细胞及其后代的质量必须在ES细胞增殖和分化的过程中得到保证。虽然仅研究了有限数量的灵长类 ES 细胞系，但很可能存在显着的系间变异。这意味着不同的 ES 细胞系在发育阶段、谱系定型、核型正常、基因表达或分化潜力方面可能有所不同。这些基因遗传和/或表观遗传诱导的变量给治疗应用带来了明显的并发症。我们的实验室从体外产生的囊胚中鉴定并分离出了恒河猴 ES 细胞系。所有测试的细胞系都具有形成多能胚状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。这篇综述文章描述了猴 ES 细胞系的衍生、未分化表型的表征，以及它们分化为谱系特异性、特别是神经表型。还讨论了灵长类 ES 细胞疗法的前景和局限性。
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.