M2 macrophage-derived exosomes for bone regeneration: A systematic review

Objective

This systematic review aims to evaluate existing evidence to investigate the therapeutic efficacy of M2 macrophage-derived exosomes in bone regeneration.

Design

A comprehensive search between 2020 and 2024 across PubMed, Web of Science, and Scopus was conducted using a defined search strategy to identify relevant studies regarding the following question: “What is the impact of M2 macrophage-derived exosomes on bone regeneration?”. Controlled in vitro and in vivo studies were included in this study. The SYRCLE tool was used to evaluate the risk of bias in the included animal studies.

Results

This review included 20 studies published. Seven studies were selected for only in vitro analysis, whereas 13 studies underwent both in vitro and in vivo analyses. The in vivo studies employed animal models, including 163 C57BL6 mice and 73 Sprague-Dawley rats. Exosomes derived from M2 macrophages were discovered to be efficacious in promoting bone regeneration and vascularization in animal models of bone defects. These effects were primarily confirmed through morphological and histological assessments. This remarkable outcome is attributed to the regulation of multiple signaling pathways, as evidenced by the findings of 11 studies investigating the involvement of miRNAs in this intricate process. In addition, in vitro studies observed positive effects on cell proliferation, migration, osteogenesis, and angiogenesis. Heterogeneity in study methods hinders direct comparison of results across studies.

Conclusion

M2 macrophage-derived exosomes demonstrate remarkable potential for promoting bone regeneration. Further research optimizing their application and elucidating the underlying mechanisms can pave the way for clinical translation.