PDX Core

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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].