Large Animal Core

项目概要-大型动物模型核心 大型动物模型核心是在上一次竞争性更新时开发的， 关注体外细胞培养系统和小动物模型并不总是很好地解决 人体健康消化道疾病问题。核心的设计是为了提供更符合生理学的模型 与人相似。在过去的5年里，CGIBD发展和加强了大型动物模型 NC州立大学兽医学院的核心，专注于医疗和外科技术 在猪身上。核心的总体目标是为中心研究者提供一个具有成本效益的中心资源 希望利用大型动物了解消化系统疾病的机制。这尤其是 对于对食管疾病感兴趣的CGIBD成员来说，这是成功的，在很大程度上是因为猪已经证明， 是嗜酸性食管炎和胃食管反流等疾病的极好转化模型 疾病猪食管与人食管一样含有食管粘膜下腺， 老鼠没有这些腺体。最近的工作通过核心已经帮助建立这些腺体作为祖细胞 来源于食道。肠缺血的疾病模型也一直是一个关键组成部分 这也是因为猪被认为在对人类的反应方面更接近人类。 缺血离体（Ussing室）和体外研究，特别是涉及大型动物复合细胞的研究 现在提供了2D和3D文化，以支持大型动物的基础科学产出。此外，委员会认为， 由于与胃肠道和微生物组相互作用有关的新想法，我们现在计划 引入非生物猪作为额外的资源。 核心的具体目标是：1）提供与核心兽医的咨询，以评估可行性， 后勤和研究设计; 2）协助动物采购，和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着良好的记录， 有资格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，麻醉和先进的成像（MRI，CT，核医学）很容易 NC State Veterinary Hospital附近的景点新装修的设施大部分由NIH G20资助 赠款是至关重要的核心的能力，提供医疗，手术和gnotobiotic能力邻近大 动物研究所基于大型动物模型核心和CGIBD资助的项目 在上一个供资期间，核心小组的目标是同时进行4-6个项目。 虽然核心目前只为少数成员服务，但它提供了显着的科学影响， 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.