Backpack-carrying macrophage immunotherapy for periodontitis

Abstract

Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy. This hurdle can be overcome by cellular backpacks (BPs), discoidal particles that adhere on the macrophage surface and regulate M1/M2 phenotypic shift in an environment-independent manner. In this study, we engineered IL-4 BPs for maintaining macrophages in the M2 phenotype to regulate excess inflammation in periodontitis, a major oral infectious disease. IL-4 BPs induced and maintained M2 phenotype in macrophages in vitro for several days. After injection of macrophages carrying IL-4 BPs into the gingiva, the cells stayed in the tissue for over 5 days and maintained the M2 phenotype in the disease sites. Furthermore, treatment with IL-4 BP-macrophages significantly suppressed the disease progression. Altogether, a treatment with BP-carrying macrophages offers a promising local therapy against periodontitis.