Progression in the In Vitro Macrophage Expansion

Macrophages play essential roles in homeostasis and disease, and they were considered terminally differentiated cells that cannot proliferate. However, growing evidence shows that macrophages can self-renew in homeostasis and multiple pathological states in vivo and artificial induction in vitro. With the rise of immune cell therapy based on macrophages, large-scale in vitro expansion of macrophages has become more and more urgent. However, the proliferation of macrophages in vitro is still inefficient because of the heterogeneity of macrophages, complicated crosstalk between macrophages and their microenvironments, and poor understanding of macrophage proliferation regulations. In this review, we summarized the discoveries known to stimulate macrophage proliferation in vitro, including cytokines, small molecule compounds, metabolites, the composition of pathogens and apoptotic cells, natural product extracts, gene editing, and other factors, as well as related mechanisms. It can be concluded that the promotion of macrophage proliferation in vitro covers various approaches and mechanisms. However, it is still necessary to test more strategies and learn more macrophage proliferation mechanisms to achieve large-scale engineering expansion of macrophages in vitro.