Pluripotent stem cell derived macrophages: current applications and future perspectives

The ability to derive macrophages from human induced pluripotent stem cells (iPSCs) provides an unlimited source of genotype-specific cells and has the potential to play an important role in advancing our understanding of macrophage biology in both homeostasis and disease. While sharing many of the functional characteristics of monocyte-derived macrophages, iPSC-derived macrophages have also been shown to have phenotypical and functional features associated with tissue resident macrophages. These features present new opportunities to develop models of human disease and to understand the role of developmental or tissue context in innate immune cell function. iPSCs-derived macrophages have also been identified as a highly attractive source for cell and gene therapy in the treatment of diverse degenerative diseases based on their capability of tissue repair functions including clearing scarred cells by phagocytosis, providing extracellular matrices and anti-inflammatory activities such as secretion of growth factors. Here, we review and present a concise discussion on macrophage differentiation from stem cells and the advantages they have over classical monocyte-derived macrophages in modelling organ specific macrophages. We summarise the various disease models utilizing iPSCs-derived macrophages including hereditary syndromes and host-pathogen interactions in tissue repair as well as various strategies including genetic programming or addition of small-molecules to mimic their pathological phenotypes. Finally, we describe the pre-clinical studies to date that have addressed the application of iPSCs-derived macrophages as a therapeutic intervention.