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.

项目摘要/摘要来自几种啮齿动物物种的稳定和嵌合体的稳定和嵌合体衍生的胚胎干细胞（ESC）革命性的现代医学。种系传播转基因ESC已成为一种力量在活啮齿动物中建模人类疾病的技术。另外，啮齿动物Esc衍生细胞的移植，组织和器官提供一个测试床，用于修复或更换人体中受损的组织和器官，用于再生医学的圣杯。但是，啮齿动物和人类之间存在很大差异在体型，寿命和生理学方面，限制了从啮齿动物中获得的见解的程度模型可以应用于人类。大型动物模型通常具有预测临床功效的能力增强相对于啮齿动物。尽管尝试了许多尝试，但善意的Esc类似于所描述的啮齿动物在任何大型动物物种中仍然没有可用。最近，我们开发了一种启用的新方法，首次，稳定和嵌合体的衍生作品从一个大型驯养的哺乳动物中逃脱了马。该提案的目的是将新开发的方法应用于稳定的推导嵌合体有能力从生物医学研究中最受欢迎的大型动物模型之一中逃脱，猪。 Chimera有能力的Pig Esc不仅会促进人类转基因猪模型的产生疾病，但还提供了一个前所未有的机会来测试胚泡的功效和安全性大型动物模型中的互补，用于体内组织和器官的移植，a 在申请人类之前的必要步骤。