Manuel Christopher A, Bagby Stacey M, Reisinger Julie A, Pugazhenthi Umarani, Pitts Todd M, Keysar Stephen B, Arcaroli John J, Leszczynski Jori K
Office of Laboratory Animal Resources, Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, University of Colorado Cancer Center, Aurora, Colorado;, Email:
School of Medicine, Division of Medical Oncology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado.
J Am Assoc Lab Anim Sci. 2017 Mar 1;56(2):166-172.
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as a model for cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retain many of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strains used to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At our institution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infected with C. bovis. Elimination of C. bovis from these colonies required the aseptic harvest and horizontal transfer of tumor tissue between infected and naïve recipient mice without cross-contamination. Out of necessity, we developed a standard operating procedure using enhancements to traditional aseptic surgical technique with concurrent application of both procedural and physical barriers to prevent C. bovis transmission. By using these methods, all 61 unique PDX tumor models were successfully harvested from C. bovis-infected mice and transferred into recipient mice without transmission of infection. Our data demonstrate that, in situations where C. bovis-free colonies can be established and maintained, this procedure can successfully be used to eliminate C. bovis from an in vivo tumor bank of valuable PDX tumors.
在免疫缺陷小鼠中传代培养的人源肿瘤异种移植（PDX）模型，正迅速成为癌症研究的常用模型。在不经过体外细胞培养的情况下，小鼠之间的水平转移使这些肿瘤能够保留其原发患者的许多独特特征。然而，用于培养这些肿瘤的免疫缺陷小鼠品系易受多种机会性病原体感染，包括牛棒状杆菌。在我们机构，两个PDX肿瘤体内库保存在裸鼠群落中，这些裸鼠群落被牛棒状杆菌感染呈地方流行性。要从这些群落中清除牛棒状杆菌，需要在无菌条件下收获肿瘤组织，并在感染小鼠和未感染的受体小鼠之间进行水平转移，同时避免交叉污染。出于需要，我们开发了一种标准操作程序，通过改进传统的无菌手术技术，并同时应用程序和物理屏障来防止牛棒状杆菌传播。通过使用这些方法，成功地从感染牛棒状杆菌的小鼠中收获了所有61种独特的PDX肿瘤模型，并将其转移到受体小鼠中，未发生感染传播。我们的数据表明，在可以建立和维持无牛棒状杆菌群落的情况下，该程序可成功用于从珍贵的PDX肿瘤体内库中清除牛棒状杆菌。
