Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing

Inspired by tumor-associated macrophages (TAMs) that produce abundant immunosuppressive and proliferative factors in tumor development, we generate macrophages to recapitulate TAMs reparative functions, by culturing normal macrophages with TAMs conditional medium (TAMs CM). These TAMs-educated macrophages (TAMEMs) outperform major macrophage phenotypes (M0, M1, or M2) in suppressing inflammation, stimulating angiogenesis, and activating fibroblasts in vitro. When delivered to skin wounds in diabetic mice, TAMEMs efficiently promote healing. Based on TAMs CM s composition, we further reconstitute a nine-factor cocktail to train human primary monocytes into TAMEMs C, which fully resemble TAMEMs functions without using tumor components, thereby having increased safety and enabling the preparation of autologous cells.