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.

中文翻译：

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用于牙周炎的背负式巨噬细胞免疫疗法


细胞免疫疗法是一种很有前途的治疗方式，可以对抗未满足的医疗需求。巨噬细胞提供了一种突出的细胞治疗方式，因为它们的表型可塑性使它们能够发挥多种作用，包括防御病原体、诱导/抑制适应性免疫和帮助伤口愈合。同时，这种可塑性是实施巨噬细胞疗法的主要障碍。细胞背包 （BP） 可以克服这一障碍，细胞背包 （BPs） 是粘附在巨噬细胞表面并以非环境性方式调节 M1/M2 表型变化的盘状颗粒。在这项研究中，我们设计了 IL-4 BPs，用于维持巨噬细胞在 M2 表型中，以调节牙周炎（一种主要的口腔传染病）中的过度炎症。IL-4 BPs 在体外诱导并维持巨噬细胞中的 M2 表型数天。将携带 IL-4 BPs 的巨噬细胞注射到牙龈后，细胞在组织中停留超过 5 天，并维持疾病部位的 M2 表型。此外，用 IL-4 BP 巨噬细胞治疗可显着抑制疾病进展。总而言之，使用携带血压的巨噬细胞治疗提供了一种很有前途的牙周炎局部疗法。