Macrophages are innate immune cells that are present in essentially all tissues, where they have vital roles in tissue development, homeostasis and pathogenesis. The importance of macrophages in tissue function is reflected by their association with various human diseases, and studying macrophage functions in both homeostasis and pathological tissue settings is a promising avenue for new targeted therapies that will improve human health. The ability to generate macrophages from induced pluripotent stem (iPS) cells has revolutionized macrophage biology, with the generation of iPS cell-derived macrophages (iMacs) providing unlimited access to genotype-specific cells that can be used to model various human diseases involving macrophage dysregulation. Such disease modelling is achieved by generating iPS cells from patient-derived cells carrying disease-related mutations or by introducing mutations into iPS cells from healthy donors using CRISPR–Cas9 technology. These iMacs that carry disease-related mutations can be used to study the aetiology of the particular disease in vitro. To achieve more physiological relevance, iMacs can be co-cultured in 2D systems with iPS cell-derived cells or in 3D systems with iPS cell-derived organoids. Here, we discuss the studies that have attempted to model various human diseases using iMacs, highlighting how these have advanced our knowledge about the role of macrophages in health and disease.

巨噬细胞是本质上存在于所有组织中的先天免疫细胞，在组织发育、体内平衡和发病机制中发挥着重要作用。巨噬细胞在组织功能中的重要性反映在它们与各种人类疾病的关联上，研究巨噬细胞在稳态和病理组织环境中的功能是改善人类健康的新靶向治疗的一个有前途的途径。从诱导多能干 (iPS) 细胞产生巨噬细胞的能力彻底改变了巨噬细胞生物学，iPS 细胞衍生的巨噬细胞 (iMac) 的产生提供了对基因型特异性细胞的无限访问，可用于模拟涉及巨噬细胞失调的各种人类疾病。这种疾病建模是通过从携带疾病相关突变的患者来源的细胞中产生 iPS 细胞，或使用 CRISPR-Cas9 技术将突变引入来自健康捐赠者的 iPS 细胞来实现的。这些携带疾病相关突变的 iMac 可用于在体外研究特定疾病的病因学。为了实现更多的生理相关性，iMac 可以在 2D 系统中与 iPS 细胞衍生的细胞共培养，或在 3D 系统中与 iPS 细胞衍生的类器官共培养。在这里，我们讨论了尝试使用 iMac 模拟各种人类疾病的研究，重点介绍了这些研究如何增进了我们对巨噬细胞在健康和疾病中的作用的了解。