(1281-B) Establishment and upscaling of iPSC-derived Macrophages differentiation protocol and comparison with other macrophage cellular models

Abstract: Macrophages play a vital role in drug discovery due to their regulatory functions in health and disease. Human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) present a valuable alternative to human monocyte-derived macrophages (MDMs), addressing issues of limited availability and donor variability. An IDMs differentiation protocol has been developed to generate large quantities of iPSC-derived macrophages suitable for medium- to high-throughput applications. These IDMs exhibit similarities to MDMs in surface marker expression such as CD14, CD206, CD163 as well as efferocytosis functions established in a high-content-imaging-based assay. Further medium and growth factor optimization of the differentiation protocol resulted in a 6-fold increase in myeloid progenitor production yield. The IDMs produced using the optimized protocol were compared to standard cell models, such as MDMs and THP-1 cells. IDMs demonstrated similarities to MDMs in terms of proinflammatory cytokine secretion under TLR4 or NOD1/2 stimulation (based on Cytokine Array and MSD assay). This improved differentiation protocol, with its higher myeloid production yield, opens new opportunities for large scale high throughput screening while employing novel macrophage cell-based assays as more physiologically relevant models.