Optimizing a five factors cocktail to prepare reparative macrophages for wound healing

To address the challenges of pathological conditions at the DFU site, in our previous study, we recapitulated the pro-regenerative and immunosuppressive functions of tumor-associated macrophages (TAMs) in non-tumor-derived macrophages, endowing the latter with characteristics for promoting diabetic wound healing - termed TAMs-educated macrophages (TAMEMs). In order to eliminate the use of tumor-derived sources and devise a more controllable method to prepare TAMEM-like cells, in this study, we identify a cocktail comprising five recombinant proteins as an essential condition to induce non-polarized macrophages (termed TAMEMs5) into therapeutic cells with pro-healing functions. These macrophages exhibited angiogenic and immunomodulatory effects in vitro and healing-promoting effects in an in vitro model of human progenitor cells.