Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Biomedical parasitology Unit, Institute Pasteur, Paris, France.
Front Immunol. 2018 Dec 13;9:2550. doi: 10.3389/fimmu.2018.02550. eCollection 2018.
Research using humanized mice has advanced our knowledge and understanding of human haematopoiesis, non-adaptive and adaptive immunity, autoimmunity, infectious disease, cancer biology, and regenerative medicine. Challenges posed by the human-malaria parasite include its complex life cycle, the evolution of drug resistance against anti-malarials, poor diagnosis, and a lack of effective vaccines. Advancements in genetically engineered and immunodeficient mouse strains, have allowed for studies of the asexual blood stage, exoerythrocytic stage and the transition from liver-to-blood stage infection, in a single vertebrate host. This review discusses the process of "humanization" of various immunodeficient/transgenic strains and their contribution to translational biomedical research. Our work reviews the strategies employed to overcome the remaining-limitations of the developed human-mouse chimera(s).
利用人源化小鼠进行的研究促进了我们对人类造血、非适应性和适应性免疫、自身免疫、传染病、癌症生物学和再生医学的认识和理解。人类疟疾寄生虫带来的挑战包括其复杂的生命周期、抗疟药物耐药性的演变、诊断不佳以及缺乏有效疫苗。基因工程和免疫缺陷小鼠品系的进步,使得在单一脊椎动物宿主中能够研究无性血阶段、红细胞外阶段以及从肝到血阶段感染的转变。这篇综述讨论了各种免疫缺陷/转基因品系的“人源化”过程及其对转化医学研究的贡献。我们的工作回顾了克服已开发出人鼠嵌合体剩余局限性所采用的策略。