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M1 macrophage-derived exosomes transfer miR-222 to induce bone marrow mesenchymal stem cell apoptosis


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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Fig. 1: Hypoxia/serum deprivation (H/SD) induces BMSC apoptosis.
Fig. 2: H/SD induces macrophage polarization toward the M1 phenotype.
Fig. 3: Effects of M1-type macrophages on the viability, migration, and apoptosis of BMSCs.
Fig. 4: Effects of M1-type macrophage-derived exosomes on the viability, migration, and apoptosis of BMSCs.
Fig. 5: M1-type macrophages transport miR-222 through exosomes to affect the viability, migration, and apoptosis of BMSCs.
Fig. 6: M1 macrophage-derived exosomes deliver miR-222 to inhibit Bcl-2 protein expression and induce BMSC apoptosis.

Data availability

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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Y. Q. performed study concept and design; Y. Q., T. Z., T. Z., X. W., W. L., and D. C. performed development of methodology and writing, review, and revision of the paper; H. M. and S. A. provided acquisition, analysis and interpretation of data, and statistical analysis; H. M. provided technical and material support. All authors read and approved the final paper.

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Correspondence to Songtao An.

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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).

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