Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes
Abstract Background Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03555-6 |
| _version_ | 1797630401145995264 |
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| author | Mengyao Liu Martin Ng Tuan Phu Laura Bouchareychas Brian T. Feeley Hubert T. Kim Robert L. Raffai Xuhui Liu |
| author_facet | Mengyao Liu Martin Ng Tuan Phu Laura Bouchareychas Brian T. Feeley Hubert T. Kim Robert L. Raffai Xuhui Liu |
| author_sort | Mengyao Liu |
| collection | DOAJ |
| description | Abstract Background Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. Methods We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. Results Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. Conclusion Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration. |
| first_indexed | 2024-03-11T11:07:43Z |
| format | Article |
| id | doaj.art-aa31497d10514eaf83e1a96d18afedc5 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-11T11:07:43Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-aa31497d10514eaf83e1a96d18afedc52023-11-12T12:08:25ZengBMCStem Cell Research & Therapy1757-65122023-11-0114111410.1186/s13287-023-03555-6Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomesMengyao Liu0Martin Ng1Tuan Phu2Laura Bouchareychas3Brian T. Feeley4Hubert T. Kim5Robert L. Raffai6Xuhui Liu7Department of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterDepartment of Veterans Affairs, San Francisco Veterans Affairs Medical CenterAbstract Background Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. Methods We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. Results Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. Conclusion Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.https://doi.org/10.1186/s13287-023-03555-6Macrophage polarizationExosomesFibro/adipogenic progenitorsBeige fat differentiationMuscle fatty infiltrationRotator cuff injury |
| spellingShingle | Mengyao Liu Martin Ng Tuan Phu Laura Bouchareychas Brian T. Feeley Hubert T. Kim Robert L. Raffai Xuhui Liu Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes Stem Cell Research & Therapy Macrophage polarization Exosomes Fibro/adipogenic progenitors Beige fat differentiation Muscle fatty infiltration Rotator cuff injury |
| title | Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes |
| title_full | Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes |
| title_fullStr | Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes |
| title_full_unstemmed | Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes |
| title_short | Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes |
| title_sort | polarized macrophages regulate fibro adipogenic progenitor fap adipogenesis through exosomes |
| topic | Macrophage polarization Exosomes Fibro/adipogenic progenitors Beige fat differentiation Muscle fatty infiltration Rotator cuff injury |
| url | https://doi.org/10.1186/s13287-023-03555-6 |
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