Monzavi Seyed Mostafa, Muhammadnejad Samad, Mansouri Vahid, Ashraf Hami, Ahmadbeigi Naser
Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
INSERM U981, Institut Gustave Roussy, Villejuif, France.
Animal Model Exp Med. 2025 Jan;8(1):20-29. doi: 10.1002/ame2.12509. Epub 2024 Nov 27.
Human-derived tumor models are essential for preclinical development of new anticancer drug entities. Generating animal models bearing tumors of human origin, such as patient-derived or cell line-derived xenograft tumors, is dependent on immunodeficient strains. Tumor-bearing immunodeficient mice are susceptible to developing unwanted disorders primarily irrelevant to the tumor nature; and if get involved with such disorders, reliability of the study results will be undermined, inevitably confounding the research in general. Therefore, a rigorous health surveillance and clinical monitoring system, along with the establishment of a strictly controlled barrier facility to maintain a pathogen-free state, are mandatory. Even if all pathogen control and biosafety measures are followed, there are various noninfectious disorders capable of causing tissue and multiorgan damage in immunodeficient animals. Therefore, the researchers should be aware of sentinel signs to carefully monitor and impartially report them. This review discusses clinical signs of common unwanted disorders in experimental immunodeficient mice, and how to examine and report them.
人源肿瘤模型对于新型抗癌药物实体的临床前开发至关重要。生成携带人源肿瘤的动物模型，如患者来源或细胞系来源的异种移植肿瘤，依赖于免疫缺陷品系。携带肿瘤的免疫缺陷小鼠易患主要与肿瘤性质无关的不良病症；如果涉及此类病症，研究结果的可靠性将受到损害，不可避免地会使整个研究产生混淆。因此，必须建立严格的健康监测和临床监测系统，并建立严格控制的屏障设施以维持无病原体状态。即使遵循所有病原体控制和生物安全措施，仍有各种非传染性病症能够在免疫缺陷动物中导致组织和多器官损伤。因此，研究人员应了解哨兵体征，以便仔细监测并公正地报告这些体征。本综述讨论了实验性免疫缺陷小鼠常见不良病症的临床体征，以及如何检查和报告这些体征。
