Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France.
Transplantation. 2020 Nov;104(11):2290-2306. doi: 10.1097/TP.0000000000003177.
The humanization of animals is a powerful tool for the exploration of human disease pathogenesis in biomedical research, as well as for the development of therapeutic interventions with enhanced translational potential. Humanized models enable us to overcome biologic differences that exist between humans and other species, while giving us a platform to study human processes in vivo. To become humanized, an immune-deficient recipient is engrafted with cells, tissues, or organoids. The mouse is the most well studied of these hosts, with a variety of immunodeficient strains available for various specific uses. More recently, efforts have turned to the humanization of other animal species such as the rat, which offers some technical and immunologic advantages over mice. These advances, together with ongoing developments in the incorporation of human transgenes and additional mutations in humanized mouse models, have expanded our opportunities to replicate aspects of human allotransplantation and to assist in the development of immunotherapies. In this review, the immune and tissue humanization of various species is presented with an emphasis on their potential for use as models for allotransplantation, graft versus host disease, and regenerative medicine.
动物的人源化是在生物医学研究中探索人类疾病发病机制以及开发具有增强转化潜力的治疗干预措施的有力工具。人源化模型使我们能够克服人类与其他物种之间存在的生物学差异，同时为我们提供了一个在体内研究人类过程的平台。要实现人源化，免疫缺陷受体被移植细胞、组织或类器官。小鼠是这些宿主中研究最广泛的，有多种免疫缺陷品系可供各种特定用途使用。最近，人们的努力转向了其他动物物种（如大鼠）的人源化，这些动物在技术和免疫学方面相对于小鼠具有一些优势。这些进展，加上在人源化小鼠模型中不断引入人类转基因和其他突变，扩大了我们复制人类同种异体移植各个方面的机会，并有助于开发免疫疗法。在这篇综述中，介绍了各种物种的免疫和组织人源化，重点介绍了它们作为同种异体移植、移植物抗宿主病和再生医学模型的潜在用途。
