Differentiation and Functional Comparison of Monocytes and Macrophages from hiPSCs with Peripheral Blood Derivatives

Abstract

A renewable source of human monocytes and macrophages would be a valuable alternative to primary cells from peripheral blood (PB) in biomedical research. We developed an efficient protocol to derive monocytes and macrophages from human induced pluripotent stem cells (hiPSCs) and performed functional comparison with PB-derived cells. hiPSC-derived monocytes were functional after cryopreservation and exhibited comparable gene expression profiles as PB-derived monocytes. Notably, hiPSC-derived monocytes were more activated with greater adhesion to endothelial cells under physiological flow. hiPSC-derived monocytes were successfully polarized to M1 and M2 macrophage subtypes that showed similar pan- and subtype-specific gene and surface protein expression and cytokine secretion to PB-derived macrophages. hiPSC-derived macrophages exhibited higher endocytosis and efferocytosis and similar bacterial and tumour cell phagocytosis functionality compared to PB-derived macrophages. In summary, we developed a robust protocol to generate hiPSC-monocytes and macrophages from independent hiPSC-lines that showed aspects of functional maturity comparable with those from PB.