Derivation of chimera competent pig embryonic stem cells under a novel condition

项目摘要/摘要 从几种啮齿动物中分离出稳定且具有嵌合体能力的胚胎干细胞 彻底改变了现代医学。转基因胚胎干细胞的生殖系传播已成为一种力量 活体啮齿动物模拟人类疾病的技术。此外，啮齿动物干细胞来源的细胞移植， 组织器官为修复或替代人体受损的组织器官提供了试验床， 再生医学的圣杯。然而，啮齿动物和人类之间有很大的不同。 在身体大小、寿命和生理学方面，这限制了从啮齿动物那里获得洞察力的程度 模型可以应用于人类。大型动物模型预测临床疗效的能力通常会增强。 相对于啮齿动物。然而，尽管多次尝试，但真正的ESC类似于 啮齿动物仍然不存在于任何大型动物物种中。最近我们开发了一种新的方法， 首次从大型驯养哺乳动物中获得稳定的、具有嵌合体能力的ESCs 马。这项建议的目的是应用新开发的方法来推导稳定的 以及来自生物医学研究中最受欢迎的大型动物模型之一的嵌合体有能力的ESCs， 那头猪。具有嵌合体能力的猪ESCs不仅将有助于生产转基因猪的人类模型 疾病，但也提供了一个前所未有的机会来测试胚泡的有效性和安全性 在体内生成移植组织和器官的大型动物模型中的互补 在人工应用之前的必要步骤。

PROJECT SUMMARY/ABSTRACT Derivation of stable and chimera competent embryonic stem cells (ESCs) from several rodent species has revolutionized modern medicine. Germline transmission of genetically modified ESCs has become a power technology for modeling human diseases in live rodents. In addition, transplantation of rodent ESC-derived cells, tissues and organs provides a testbed for repairing or replacing damaged tissues and organs in the human body, a holy grail for regenerative medicine. However, there are considerable differences between rodents and humans in terms of body size, lifespan and physiology, which limit the degree to which insights derived from the rodent models can be applied to humans. Large animal models often have an enhanced ability to predict clinical efficacy relative to rodents. Despite numerous attempts, however, bona fide ESC analogous to those described for rodents are still not available in any large animal species. Recently we developed a new method that enabled, for the first time, the derivation of stable and chimera competent ESCs from a large domesticated mammal, the horse. The objective of this proposal is to apply the newly developed method for the derivation of stable and chimera competent ESCs from one of the most popular large animal models in biomedical research, the pig. Chimera competent pig ESCs will not only facilitate the production of transgenic pig models of human diseases but also provide an unprecedented opportunity to test the efficacy and safety of blastocyst complementation in a large animal model for in vivo generation of tissues and organs for transplantation, a necessary step prior to human applications.