PDX Core

摘要： UP-PDTC的PDX核心是广泛异种移植的主要实验实验室 宾夕法尼亚大学(UPenn)的课程。对人类癌症的研究越来越依赖于 关于将人类组织移植到高度免疫受损的小鼠品系中，这些品系允许各种 人性化程度。这些车型的数量和类型都在继续增加。在过去的几年里 几十年来，研究人员已经开发出缺乏T、B或NK细胞功能的模型，如NOD.Cg- Prkdcsord Il2rgtm1Wjl/Szj(Nsg)[1]，类似的NOD.Cg-Prkdcsord Il2rgtm1Sug/JicTac(NOG)[2]以及小鼠 在此背景下产生的转基因被引入以允许表达人类生长因子或 能促进人体组织植入、生长或功能的细胞因子。在其他情况下，移植 包括胎儿骨髓、肝脏和胸腺(BLT)在内的多种人体组织的联合移植允许增强功能 使用所谓的BLT小鼠模型进行移植组织的研究[3]。尽管有相对较少的详细说明 对这些菌株的动物护理要求的学术描述，多个出版物已经证明 这些菌株很容易感染，这种感染可以改变人体组织或 人体组织植入后的行为影响实验的重复性和稳健性[4-8]。是这样的 感染会影响研究实验的结果，这种缺乏重复性和高 维护这些小鼠品系的成本限制了它们的适应和使用。在宾夕法尼亚大学，我们已经解决了 通过开发特定的核心设施-干细胞和异种移植核心(SCXC)来关注这一问题，该中心专注于 关于高度免疫缺陷小鼠品系的维护和促进研究。如下所示，我们 已经得到了广泛的接受，并越来越多地使用我们的专业知识和设施，许多研究人员适应了 尤其是患者来源的异种移植(PDX)模型。这一成功在很大程度上是由于孤立的 间隔室，制定设施特定的标准操作程序，以及高度熟练和训练有素的人员 人事部。宾夕法尼亚大学允许我们改装并使用斯米洛翻译中心的6个房间的套房 研究大楼。这间套房内的通道和畜牧业由我们的动物工作人员控制。所有用户 必须经过培训才能进入SCXC动物套间，并且必须遵守严格的无菌规则。这间套房是 定期对所有设备进行清洁和去污维护。利用这个空间 在这些指南中，SCXC内的动物使用已经增加到我们提供900 每月向用户发送动物；空间占有率目前为预测最大容量的85%。 重要的是，我们预计动物用途将继续增长，因为我们已经帮助创造了我们自己的老鼠品系 使用在我们的套件中执行的转基因程序，早期采用和描述未发表的 小鼠品系(NSG-IL6)和复杂小鼠品系的预期到来，如MISTRG小鼠[9， 10]。

Summary: The PDX Core of the UP-PDTC is the primary experimental laboratory of the extensive xenotransplantation program at the University of Pennsylvania (UPENN). Research into human cancers is increasingly dependent on the transplantation of human tissues into highly immunocompromised mouse strains that allow various degrees of humanization. The number and type of these models continues to increase. Over the last few decades, researchers have developed models that lack T, B or NK cell function such as the NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ (NSG)[1], the similar NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) [2] as well as mice generated on this background with transgenes introduced to allow for expression of human growth factors or cytokines that can enhance the engraftment, growth or function of human tissues. In other cases, transplantation of multiple human tissues including fetal bone marrow, liver and thymus (BLT) allows for enhanced functionality of engrafted tissue using the so called BLT mouse model[3]. Although there is relatively little by way of detailed academic descriptions of the animal care requirements of these strains, multiple publications have demonstrated that these strains are prone to infections and that such infections can change engraftment of human tissues or behavior of human tissues after engraftment affecting experimental reproducibility and robustness [4-8]. Such infections can impact on outcome of research experiments and this lack of reproducibility combined with the high cost of maintaining these mouse strains has limited their adaptation and use. At UPENN, we have addressed this concern by developing a specific Core facility, the Stem Cell and Xenograft Core (SCXC), which is focused on maintenance of highly immunocompromised mouse strains and facilitating research. As shown below, we have had wide acceptance and increasing use of our expertise and facility with numerous researchers adapting patient-derived xenograft (PDX) models in particular. This success is due largely to a combination of an isolated vivarium suite, development of facility specific standard operating procedures, and highly skilled and trained personnel. UPENN has allowed us to adapt and utilize a 6 room suite in the Smilow Center for Translational Research Building. Access to and animal husbandry within this suite is controlled by our animal staff. All users must undergo training to access the SCXC animal suite and must adhere to strict sterility rules. The suite is maintained using frequent cleaning and decontamination of all equipment on a routine basis. Using this space and these guidelines, the animal use within the SCXC has increased to the point where we are providing 900 animals per month to users; space occupancy is currently running at 85% of predicted maximal capacity. Importantly, we anticipate continued growth of animal use as we have helped to create our own mouse strains using transgenic procedures performed within our suite, early adoption and characterization of unpublished mouse strains (NSG-IL6) and the anticipated arrival of complex mouse strains such as the MISTRG mouse[9, 10].