Abstract
Aim
Our current study is conducted with intention to explore the regulatory mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicle (EV)-miR-744-5p in glioma.
Methods
Expression patterns of TGFB1, TGFBR1, and miR-744-5p were determined. EVs were isolated from human MSCs, which were characterized. Then, macrophages were co-cultured with MSCs with ectopic miR-744-5p expression to explore its role in cell proliferation, invasion, and migration capabilities. A nude mouse model of glioma xenograft was developed to observe the tumorigenesis and metastasis ability of glioma in vivo.
Results
TGFB1 and TGFBR1 were upregulated in glioma. TGFB1 promoted M2 polarization of macrophages through theMAPK signaling, thereby promoting the progression of glioma. MSC-EVs suppressed TGFB1 expression in macrophages and inhibited M2 polarization of macrophages. MSC-EVs-miR-744-5p/TGFB1/MAPK axis inhibited M2 polarization of macrophages and reduced the malignant phenotypes of glioma cells. In vivo experiments verified that MSC-EVs-miR-744-5p inhibited the polarization of macrophage M2 and prevented glioma progression.
Conclusion
Taken together, MSC-EVs-miR-744-5p may suppress the MAPK signaling activity by downregulating TGFB1, and then inhibit polarization of macrophages M2, thereby preventing the progression of glioma.
Graphical abstract
Graphical Headlights 1. TGFB1 promotes the M2 polarization of macrophages via the MAPK signaling. 2. miR-744-5p carried by MSC-EVs targets and inhibits TGFB1. 3. MSC-EV-miR-744-5p inhibits M2 polarization of macrophages to prevent glioma progression. 4. miR-744-5p loaded by MSC-EVs may be a preventive strategy against glioma.
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This study was supported by the Science & Technology Department of Sichuan Province (No. 2021YJ0179).
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Conceived and designed the experiments: LL, MXC. Performed experimental: LL, MXC. Performed experimental validation: TZ, YC. Analyzed the data and conceived figures and tables: YQW, QW. Wrote the paper: LL, MXC. Contributed to the writing of the manuscript: YQW, QW. All authors revised and approved the final version of the manuscript.
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The study protocol was performed with the Helsinki Declaration and approved by the Medical and Clinical Research Ethics Committee of Sichuan Provincial People’s Hospital. All operations involving nude mice have been approved by the Animal Care and Use Committee of Sichuan Provincial People’s Hospital.
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Liu, L., Cheng, M., Zhang, T. et al. Mesenchymal stem cell-derived extracellular vesicles prevent glioma by blocking M2 polarization of macrophages through a miR-744-5p/TGFB1-dependent mechanism. Cell Biol Toxicol 38, 649–665 (2022). https://doi.org/10.1007/s10565-021-09652-7
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DOI: https://doi.org/10.1007/s10565-021-09652-7