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

在新条件下衍生嵌合体感受态猪胚胎干细胞

基本信息

批准号：
10205187
负责人：
Jun Wu
金额：
$ 28.81万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10205187
关键词：
Anatomy Animal Model Animals Biomedical Research Blood Vessels Body Size Cell Differentiation process Cell Line Cells Chimera organism Communities Competence Complement DNA Derivation procedure Development Disabled Persons Disease model ES Cell Line Elements Embryo Embryonic Development Equus caballus Event Eye Family suidae Fetal Heart Fetus Funding Generations Genome Genome engineering Goals Grant Human Human body In Vitro Kidney Knock-in Knock-out Label Longevity Mammals Methodology Methods Modeling Modern Medicine Monitor Mouse Cell Line Mus Organ Organ Donor Organ Transplantation Organogenesis Pancreas Physiology Pluripotent Stem Cells Production Rattus Regenerative Medicine Research Rodent Rodent Model Safety Somatic Cell Source Structure of primordial sex cell Technology Thymus Gland Time Tissues Transgenic Organisms Transplantation United States National Institutes of Health Work Xenograft procedure base blastocyst clinical efficacy clinical predictors efficacy testing embryonic stem cell engineered nucleases genome editing genomic locus human disease human model in vivo in vivo Model insight interest novel pluripotency porcine model pre-clinical progenitor repaired scale up self-renewal somatic cell nuclear transfer success trait transmission process

项目摘要

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.

项目总结/摘要从几种啮齿动物中获得稳定的嵌合体胚胎干细胞（ESC），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动力在活体啮齿动物中模拟人类疾病的技术。此外，啮齿动物ESC衍生细胞的移植，组织和器官为修复或替换人体内受损的组织和器官提供了试验平台，再生医学的圣杯然而，啮齿类动物和人类之间有相当大的差异在体型、寿命和生理方面，这限制了从啮齿动物身上获得见解的程度。模型可以应用于人类。大型动物模型通常具有增强的预测临床疗效的能力相对于啮齿动物。然而，尽管进行了许多尝试，但真正的ESC类似于啮齿类动物仍然没有任何大型动物物种。最近我们开发了一种新方法，这是第一次，从大型驯养哺乳动物中获得稳定的嵌合体ESC，马本建议的目的是应用新开发的方法推导稳定的以及来自生物医学研究中最流行的大型动物模型之一的嵌合体胜任的ESC，猪。嵌合体感受态猪胚胎干细胞不仅有利于人类转基因猪模型的产生，同时也提供了一个前所未有的机会来测试囊胚的有效性和安全性在用于体内产生用于移植的组织和器官的大型动物模型中的互补，这是人类应用前的必要步骤。