Novartis, Novartis Institutes for BioMedical Research, Preclinical Safety, Cambridge, Massachusetts 02139, USA.
Novartis, Novartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
ILAR J. 2020 Dec 31;61(2-3):139-166. doi: 10.1093/ilar/ilab017.
Biomedical research involving animal models continues to provide important insights into disease pathogenesis and treatment of diseases that impact human health. In particular, nonhuman primates (NHPs) have been used extensively in translational research due to their phylogenetic proximity to humans and similarities to disease pathogenesis and treatment responses as assessed in clinical trials. Microscopic changes in tissues remain a significant endpoint in studies involving these models. Spontaneous, expected (ie, incidental or background) histopathologic changes are commonly encountered and influenced by species, genetic variations, age, and geographical origin of animals, including exposure to infectious or parasitic agents. Often, the background findings confound study-related changes, because numbers of NHPs used in research are limited by animal welfare and other considerations. Moreover, background findings in NHPs can be exacerbated by experimental conditions such as treatment with xenobiotics (eg, infectious morphological changes related to immunosuppressive therapy). This review and summary of research-relevant conditions and pathology in rhesus and cynomolgus macaques, baboons, African green monkeys, common marmosets, tamarins, and squirrel and owl monkeys aims to improve the interpretation and validity of NHP studies.
涉及动物模型的生物医学研究继续为疾病发病机制和影响人类健康的疾病治疗提供重要见解。特别是,由于非人类灵长类动物(NHPs)与人类在进化上的亲缘关系密切,并且在临床试验中评估的疾病发病机制和治疗反应相似,因此它们被广泛用于转化研究。组织中的微观变化仍然是这些模型研究的重要终点。自发的、预期的(即偶发的或背景的)组织病理学变化很常见,并且受到物种、遗传变异、年龄和动物的地理来源的影响,包括接触传染性或寄生虫病原体。通常,背景发现会使与研究相关的变化变得复杂,因为用于研究的 NHPs 的数量受到动物福利和其他因素的限制。此外,实验条件(例如用外源化学物质治疗)会加剧 NHPs 中的背景发现,例如与免疫抑制治疗相关的传染性形态变化。本综述和总结了恒河猴和食蟹猴、狒狒、绿长尾猴、普通狨猴、绢毛猴和松鼠猴及吼猴中与研究相关的条件和病理学,旨在提高 NHPs 研究的解释和有效性。