In the myocardial infarction microenvironment, the effect of macrophages on the function of bone marrow mesenchymal stem cells (BMSCs) is unclear. In this study, we investigated the role of hypoxia/serum deprivation (H/SD)-induced M1-type macrophage-derived exosomes on BMSC viability, migration, and apoptosis. We found that H/SD reduced BMSC viability and migration, increased BMSC apoptosis, and induced macrophage polarization toward the M1 phenotype. BMSCs were cultured by the supernatant of H/SD-induced THP-1 cells (M1-type macrophages) with or without exosome inhibitor treatment. The results show that BMSC apoptosis is increased in the H/SD-induced THP-1 cell supernatant group and is decreased by GM4869 treatment, indicating that M1-type macrophages induce BMSC apoptosis through exosomes. In addition, we confirm that miR-222 plays an important role in promoting BMSC apoptosis by targeting B-cell lymphoma (Bcl)-2. M1-type macrophage-derived exosomes significantly decrease BMSC viability and migration and increase BMSC apoptosis, and these effects are partly abolished by a miR-222 inhibitor. Our findings suggest that under H/SD conditions, exosomes derived from M1-type macrophages can induce BMSC apoptosis by delivering miR-222 to BMSCs.
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The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
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This study was supported by National Nature Science Foundation of China (General Program; Grant number 81970312) and Natural Science Foundation of Henan Province (Grant number 182300410304).
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Qi, Y., Zhu, T., Zhang, T. et al. M1 macrophage-derived exosomes transfer miR-222 to induce bone marrow mesenchymal stem cell apoptosis. Lab Invest 101, 1318–1326 (2021). https://doi.org/10.1038/s41374-021-00622-5