Mice with severe immunodeficiencies have become very important tools for studying foreign cells in an in vivo environment. Xenotransplants can be used to model cells from many species, although most often, mice are humanized through the transplantation of human cells or tissues to meet the needs of medical research. The development of immunodeficient mice is reviewed leading up to the current state-of-the-art strains, such as the NOD-scid-gamma (NSG) mouse. NSG mice are excellent hosts for human hematopoietic stem cell transplants or immune reconstitution through transfusion of human peripheral blood mononuclear cells. However, barriers to full hematopoietic engraftment still remain; notably, the survival of human cells in the circulation is brief, which limits overall hematological and immune reconstitution. Reports have indicated a critical role for monocytic cells – monocytes, macrophages, and dendritic cells – in the clearance of xenogeneic cells from circulation. Various aspects of the NOD genetic background that affect monocytic cell growth, maturation, and function that are favorable to human cell transplantation are discussed. Important receptors, such as SIRPα, that form a part of the innate immune system and enable the recognition and phagocytosis of foreign cells by monocytic cells are reviewed. The development of humanized mouse models has taken decades of work in creating more immunodeficient mice, genetic modification of these mice to express human genes, and refinement of transplant techniques to optimize engraftment. Future advances may focus on the monocytic cells of the host to find ways for further engraftment and survival of xenogeneic cells.

中文翻译：

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免疫缺陷小鼠人源化的单核细胞障碍

患有严重免疫缺陷的小鼠已成为在体内环境中研究外来细胞的非常重要的工具。异种移植可用于对许多物种的细胞进行建模，但最常见的是，通过移植人类细胞或组织来使小鼠人性化，以满足医学研究的需要。对免疫缺陷小鼠的发育进行了回顾，最终形成了当前最先进的品系，例如 NOD-scid-gamma (NSG) 小鼠。NSG 小鼠是人类造血干细胞移植或通过输注人外周血单核细胞进行免疫重建的优良宿主。然而，完全造血移植的障碍仍然存在；值得注意的是，人体细胞在循环中的存活时间很短，这限制了整体血液学和免疫重建。报告表明，单核细胞（单核细胞、巨噬细胞和树突细胞）在清除循环中的异种细胞方面发挥着关键作用。讨论了影响单核细胞生长、成熟和有利于人类细胞移植的功能的 NOD 遗传背景的各个方面。重要的受体，如 SIRPα，构成先天免疫系统的一部分，并使单核细胞能够识别和吞噬外来细胞。人源化小鼠模型的开发花费了数十年的时间来创造更多的免疫缺陷小鼠，对这些小鼠进行基因改造以表达人类基因，并改进移植技术以优化植入。未来的进展可能集中在宿主的单核细胞上，以寻找异种细胞进一步植入和存活的方法。