MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs
Abstract Background Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study,...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-02429-0 |
| _version_ | 1797219576844386304 |
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| author | Huasheng Lai Hon-Chi Yip Yu Gong Kai-Fung Chan Kevin Kai-Chung Leung Melissa Shannon Chan Xianfeng Xia Philip Wai-Yan Chiu |
| author_facet | Huasheng Lai Hon-Chi Yip Yu Gong Kai-Fung Chan Kevin Kai-Chung Leung Melissa Shannon Chan Xianfeng Xia Philip Wai-Yan Chiu |
| author_sort | Huasheng Lai |
| collection | DOAJ |
| description | Abstract Background Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC−Exo) for the prevention of esophageal stenosis after ESD in a porcine model. Results Pigs were randomly assigned into (1) ChGelMSC−Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC–MS/MS) and small RNA sequencing. ChGelMSC−Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFβ1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. Conclusions Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD. Graphical Abstract |
| first_indexed | 2024-04-24T12:35:51Z |
| format | Article |
| id | doaj.art-22ddc710e254412c99fc5774b409dbbf |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-24T12:35:51Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-22ddc710e254412c99fc5774b409dbbf2024-04-07T11:29:18ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122112410.1186/s12951-024-02429-0MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigsHuasheng Lai0Hon-Chi Yip1Yu Gong2Kai-Fung Chan3Kevin Kai-Chung Leung4Melissa Shannon Chan5Xianfeng Xia6Philip Wai-Yan Chiu7Department of Gastroenterology and Hepatology, Guangzhou Key Laboratory of Digestive Diseases, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of TechnologyDepartment of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong KongDepartment of Endoscopy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterDepartment of Biomedical Engineering, The Chinese University of Hong KongDepartment of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong KongDepartment of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong KongDepartment of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong KongDepartment of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong KongAbstract Background Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC−Exo) for the prevention of esophageal stenosis after ESD in a porcine model. Results Pigs were randomly assigned into (1) ChGelMSC−Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC–MS/MS) and small RNA sequencing. ChGelMSC−Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFβ1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. Conclusions Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02429-0Mesenchymal stem cellsExosomesMFGE8Endoscopic submucosal dissectionEsophageal stricture |
| spellingShingle | Huasheng Lai Hon-Chi Yip Yu Gong Kai-Fung Chan Kevin Kai-Chung Leung Melissa Shannon Chan Xianfeng Xia Philip Wai-Yan Chiu MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs Journal of Nanobiotechnology Mesenchymal stem cells Exosomes MFGE8 Endoscopic submucosal dissection Esophageal stricture |
| title | MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs |
| title_full | MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs |
| title_fullStr | MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs |
| title_full_unstemmed | MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs |
| title_short | MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs |
| title_sort | mfge8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs |
| topic | Mesenchymal stem cells Exosomes MFGE8 Endoscopic submucosal dissection Esophageal stricture |
| url | https://doi.org/10.1186/s12951-024-02429-0 |
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