DERIVATION AND SAFETY TESTING OF NON-HUMAN PRIMATE EMBRYONIC GERM CELL LINES

目前已有两种类型的多能干细胞，即胚胎干细胞和胚胎生殖细胞。 从人类和小鼠的胚胎和胎儿发育而来。胚胎干细胞来源于植入前的 而EG细胞来自胎儿性腺中的原始生殖细胞(PGCs)。这样的全能 干细胞能够分化为多种类型的细胞，是一种重要的新资源 用于治疗人类疾病。由多能干细胞产生的分化细胞可能是潜在的 用于治疗多种人类疾病，包括阿尔茨海默氏症、帕金森氏症、糖尿病、中风和心脏病 疾病。但关于基因组印迹的生长、正常分化、稳定性和 干细胞的潜在肿瘤形成需要在它们可以用于临床之前被解决。技术和 伦理障碍排除了使用人类胚胎干细胞或胚胎干细胞直接解决其中许多问题的可能性。 因此，这些问题中的许多将需要在临床前动物模型中进行研究。中美之间的差异 小鼠和人ES、EG细胞生长特性、标志物表达及基因印迹状态 这表明，对于所有的临床前研究来说，小鼠可能并不是最合适的模型。ES和EG的研究 与人类关系密切的灵长类物种中的细胞可以帮助填补我们关于效用和 基于细胞的疗法的安全性。虽然ES细胞是从非人灵长类动物(NHP)发展而来的，但在那里 目前还没有关于试图从非人类灵长类动物中产生EG细胞的报道。在这里，我们建议推导出 灵长类EG细胞及其生长、分化能力和标志物表达的比较 灵长类ES细胞以及人类ES和EG细胞。灵长类ES和EG细胞系随后将被用于分析 目前不能用人类干细胞解决的问题。这些问题包括这种干细胞是否可以 正常分化为胚胎中的所有细胞系，干细胞是否会在 移植，以及是否存在改变的基因组印记，以及它们是否对干细胞构成重大障碍 移植。这项建议的目的是为了填补我们在有效性和安全性方面的知识空白。 多能干细胞在基于细胞的疗法中的应用。

Two types of pluripotent stem cells, embryonic stem (ES) cells and embryonic germ (EG) cells have been developed from human and murine embryos and fetuses. ES cells are derived from the pre-implantation blastocyst whereas EG cells are derived from primordial germ cells (PGCs) in the fetal gonad. Such pluripotent stem cells are capable of differentiating into a wide variety of cell types and represent an important new resource for the treatment of human diseases. Differentiated cells produced from pluripotent stem cells could potentially be used to treat a wide variety of human diseases including Alzheimer's, Parkinson's, diabetes, stroke and heart disease. But major questions about the growth, normal differentiation, stability of genomic imprints and potential for tumor formation of stem cells need to be addressed before they can be used clinically. Technical and ethical barriers preclude many of these questions being addressed directly using human ES or EG cells. Therefore, many of these questions will need to be studied in pre-clinical animal models. Differences in the growth characteristics, marker expression and gene imprinting status of murine and human ES and EG cells suggest that mice might not represent the most appropriate model for all pre-clinical studies. Studies of ES and EG cells in primate species closely related to humans could help fill gaps in our knowledge concerning the utility and safety of cell-based therapies. Whereas ES cells have been developed from non-human primates (nhp), there have been no reports of attempts to generate EG cells from non-human primates. Here we propose to derive primate EG cells and to compare their growth, differentiation capacity and marker expression with existing primate ES cells and with human ES and EG cells. Primate ES and EG cell lines will then be used to analyze questions that cannot currently be addressed using human stem cells. These include whether such stem cells can differentiate normally into all cell lineages in the embryo, whether stem cells will form tumors upon transplantation and whether altered genomic imprints exist and if they present a significant barrier to stem cell transplantation. The goals of this proposal are designed to fill gaps in our knowledge of the usefulness and safety of pluripotent stem cells in cell-based therapies.