Large Animal Core

项目摘要-大型动物模型核心 大型动物模型核心是在上一次竞争更新时开发的，以解决 担心体外细胞培养系统和小动物模型并不总是很好地转化为解决 人类健康的消化系统疾病问题。核心设计是为了提供更具生理学意义的模型 与人类相似。在过去的5年里，CGIBD开发和加强了一个大型动物模型 北卡罗来纳州州立大学兽医学院的核心专业是医疗和外科技术 在猪身上。核心的总体目标是为中心调查人员提供具有成本效益的中央资源 希望利用大型动物了解消化系统疾病的机制。这一次尤其是 对于对食道疾病感兴趣的CGIBD成员来说是成功的，很大程度上是因为猪已经证明 是嗜酸性食管炎和胃食道反流等疾病的优秀翻译模型 疾病。猪的食道和人的食道一样含有食道粘膜下腺，而 老鼠缺少这些腺体。最近通过核心的研究帮助建立了这些腺体作为祖细胞 来源在食道。肠道缺血的疾病模型也一直是一个关键组成部分 也是因为猪被认为在反应方面更像人类 缺血症。体外(Ussing小室)和体外研究，特别是涉及大型动物复杂细胞的研究 现在正在提供文化(2D和3D)来支持大型动物的基础科学成果。此外， 由于与胃肠道和微生物群相互作用相关的新想法，我们现在计划 引入灵知生猪作为额外资源。 CORE的具体目标是：1)与CORE兽医提供咨询，以评估可行性， 后勤和研究设计；2)协助动物采购，3)协调动物程序， 包括麻醉、内窥镜检查和手术。 核心董事(Blikslager和Gonzalez)在消化系统疾病方面有良好的记录，并 拥有董事会认证的外科兽医专家。兽医委员会认证的实验动物专家 医学、内科医学、麻醉和高级成像(MRI、CT、核医学)都很容易 可从北卡罗来纳州州立兽医医院购买。新翻修的设施很大程度上是由NIH G20资助的 Grant是核心提供医疗、手术和灵知生物能力的关键，邻近于大型 动物研究室。基于与大型动物模型CORE和CGIBD共同开发的资助项目 调查人员在之前的资助期间，核心项目的目标是在任何时候都有4-6个项目在运行。 尽管核心目前服务于少数成员，但它在以下方面提供了显著的科学影响 他们的研究没有核心是不可能的。

PROJECT SUMMARY - LARGE ANIMAL MODELS CORE The Large Animal Models Core was developed at the time of the last competing renewal to address the concern that in vitro cell culture systems and small animal models have not always translated well to solving human health digestive disease problems. The core was designed to provide models more physiologically similar to people. Over the past 5-years, the CGIBD has developed and strengthened a Large Animal Models Core at the NC State University College of Veterinary Medicine focused on medical and surgical technologies in pigs. The overall goal of the core is to provide a cost-effective central resource for Center investigators wishing to understand mechanisms of digestive disease using large animals. This has been particularly successful for CGIBD members interested in esophageal disease, in large part because the pig has proven to be an excellent translational model of diseases such as eosinophilic esophagitis and gastroesophageal reflux disease. The pig esophagus contains esophageal submucosal glands as does the human esophagus, while mice lack these glands. Recent work through the core has helped to establish these glands as a progenitor cell source in the esophagus. Disease models of intestinal ischemia have also continued to be a critical component of the Core, again because pigs are thought to more closely resemble humans in terms of their response to ischemia. Ex vivo (Ussing chambers) and in vitro studies, particularly those involving large animal complex cell culture (2D and 3D) are now being offered to bolster the basic science output from large animals. Furthermore, because of novel ideas related to the interaction of the gastrointestinal tract and the microbiome, we now plan to introduce gnotobiotic pigs as an additional resource. The specific aims of the core are: 1) to provide consultation with Core veterinarians to assess feasibility, logistics and study design; 2) to assist with procurement of animals, and 3) to coordinate animal procedures, including anesthesia, endoscopy, and surgery. The Core directors (Blikslager and Gonzalez) have a demonstrated track record in digestive disease and are board-certified veterinary specialists in surgery. Veterinary board-certified specialists in laboratory animal medicine, internal medicine, anesthesia, and advanced imaging (MRI, CT, nuclear medicine) are readily available from the NC State Veterinary Hospital. Newly renovated facilities funded in large part by an NIH G20 grant are crucial to the Core’s ability to offer medical, surgical and gnotobiotic capabilities adjacent to large animal research housing. Based on funded projects developed with the Large Animal Models Core and CGIBD investigators during the prior funded period, the Core will aim to have 4-6 projects running at any one time. Although the Core currently serves a small number of members, it provides a remarkable scientific impact on their research which would not be possible without the core.