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

非人类灵长类胚胎生殖细胞系的衍生和安全性测试

• 批准号: 7714978
• 负责人: PETER John DONOVAN
• 金额: $ 62.33万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7714978
• 关键词: Address; Affect; Alzheimer' s Disease; Animal Model; Cell Differentiation process; Cell Lineage; Cell Therapy; Cells; Characteristics; Chimera organism; Condition; Derivation procedure; Development; Diabetes Mellitus; Differentiation and Growth; Disadvantaged; EG Cell Line; Embryo; Foundations; Gene Expression; Genes; Genome Stability; Genomic Imprinting; Germ; Germ Cells; Goals; Gonadal structure; Growth; Heart Diseases; Human; Immunodeficient Mouse; In Vitro; Knowledge; Maintenance; Modeling; Monkeys; Mus; Parkinson Disease; Pluripotent Stem Cells; Population; Primates; Reagent; Reporting; Resources; Role; Safety; Stem cell transplant; Stem cells; Stroke; Structure of primordial sex cell; System; Techniques; Testing; Transplantation; cell type; design; embryo/fetus; embryonic stem cell; fetal; human disease; human stem cells; imprint; in vivo; natural Blastocyst Implantation; nonhuman primate; pluripotency; pre-clinical; preclinical study; stem; tumor

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.

两种类型的多能干细胞，胚胎干（ES）细胞和胚胎生殖（EG）细胞已经被研究。 由人类和鼠类胚胎和胎儿发育而成。ES细胞来源于植入前 胚泡，而EG细胞来源于胎儿性腺中的原始生殖细胞（PGCs）。如此多能 干细胞能够分化成多种细胞类型，是一种重要的新资源 用于治疗人类疾病。从多能干细胞产生的分化细胞可能是 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 疾病但是，关于生长、正常分化、基因组印记的稳定性以及 在干细胞用于临床之前，需要解决它们形成肿瘤的潜力。技术和 伦理上的障碍阻碍了直接使用人ES或EG细胞来解决这些问题中的许多问题。 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。差异 小鼠和人ES和EG细胞的生长特性、标志物表达和基因印迹状态 提示小鼠可能不是所有临床前研究的最合适模型。ES和EG的研究 与人类密切相关的灵长类动物的细胞可以帮助填补我们关于实用性的知识空白， 细胞疗法的安全性。尽管ES细胞是从非人灵长类动物（nhp）中开发出来的， 还没有尝试从非人灵长类动物产生EG细胞的报道。在这里，我们建议导出 灵长类EG细胞，并比较它们的生长，分化能力和标记物表达与现有的 灵长类ES细胞和人ES和EG细胞。然后将使用灵长类ES和EG细胞系分析 这些问题目前还不能用人类干细胞来解决。这些问题包括这些干细胞是否可以 在胚胎中正常分化为所有细胞谱系，干细胞是否会在胚胎中形成肿瘤， 是否存在改变的基因组印记，以及它们是否对干细胞移植存在显著障碍。 移植该提案的目的是填补我们对有效性和安全性的知识空白。 多能干细胞在细胞治疗中的应用。