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MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.
Lai, Huasheng; Yip, Hon-Chi; Gong, Yu; Chan, Kai-Fung; Leung, Kevin Kai-Chung; Chan, Melissa Shannon; Xia, Xianfeng; Chiu, Philip Wai-Yan.
Afiliación
  • Lai H; Department 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 Technology, Guangzhou, 510180, People's Republic of China.
  • Yip HC; Department of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
  • Gong Y; Department of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
  • Chan KF; Department of Endoscopy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
  • Leung KK; Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
  • Chan MS; Chow Yuk Ho Technology Center for Innovative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
  • Xia X; Department of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
  • Chiu PW; Department of Surgery and State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, 999077, People's Republic of China.
J Nanobiotechnology ; 22(1): 143, 2024 Apr 01.
Article en En | MEDLINE | ID: mdl-38561800
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 TGFß1 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estenosis Esofágica / Exosomas / Células Madre Mesenquimatosas / Resección Endoscópica de la Mucosa Límite: Animals Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estenosis Esofágica / Exosomas / Células Madre Mesenquimatosas / Resección Endoscópica de la Mucosa Límite: Animals Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido