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Exosomes derived from mesenchymal stem cells inhibit neointimal hyperplasia by activating the Erk1/2 signalling pathway in rats.
Liu, Zhihui; Wu, Chao; Zou, Xinliang; Shen, Weiming; Yang, Jiacai; Zhang, Xiaorong; Hu, Xiaohong; Wang, Haidong; Liao, Yi; Jing, Tao.
Afiliação
  • Liu Z; Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
  • Wu C; State Key Laboratory of Silkworm Genome Biology, The Institute of Sericulture and Systems Biology, Southwest University, Chongqing, China.
  • Zou X; State Key Laboratory of Silkworm Genome Biology, The Institute of Sericulture and Systems Biology, Southwest University, Chongqing, China.
  • Shen W; Department of Thoracic Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  • Yang J; Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
  • Zhang X; Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Hu X; The Institute of Burn Research, South-West Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  • Wang H; The Institute of Burn Research, South-West Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  • Liao Y; The Institute of Burn Research, South-West Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  • Jing T; Department of Thoracic Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Stem Cell Res Ther ; 11(1): 220, 2020 06 08.
Article em En | MEDLINE | ID: mdl-32513275
BACKGROUND: Restenosis is a serious problem in patients who have undergone percutaneous transluminal angioplasty. Endothelial injury resulting from surgery can lead to endothelial dysfunction and neointimal formation by inducing aberrant proliferation and migration of vascular smooth muscle cells. Exosomes secreted by mesenchymal stem cells have been a hot topic in cardioprotective research. However, to date, exosomes derived from mesenchymal stem cells (MSC-Exo) have rarely been reported in association with restenosis after artery injury. The aim of this study was to investigate whether MSC-Exo inhibit neointimal hyperplasia in a rat model of carotid artery balloon-induced injury and, if so, to explore the underlying mechanisms. METHODS: Characterization of MSC-Exo immunophenotypes was performed by electron microscopy, nanoparticle tracking analysis and western blot assays. To investigate whether MSC-Exo inhibited neointimal hyperplasia, rats were intravenously injected with normal saline or MSC-Exo after carotid artery balloon-induced injury. Haematoxylin-eosin staining was performed to examine the intimal and media areas. Evans blue dye staining was performed to examine re-endothelialization. Moreover, immunohistochemistry and immunofluorescence were performed to examine the expression of CD31, vWF and α-SMA. To further investigate the involvement of MSC-Exo-induced re-endothelialization, the underlying mechanisms were studied by cell counting kit-8, cell scratch, immunofluorescence and western blot assays. RESULTS: Our data showed that MSC-Exo were ingested by endothelial cells and that systemic injection of MSC-Exo suppressed neointimal hyperplasia after artery injury. The Evans blue staining results showed that MSC-Exo could accelerate re-endothelialization compared to the saline group. The immunofluorescence and immunohistochemistry results showed that MSC-Exo upregulated the expression of CD31 and vWF but downregulated the expression of α-SMA. Furthermore, MSC-Exo mechanistically facilitated proliferation and migration by activating the Erk1/2 signalling pathway. The western blot results showed that MSC-Exo upregulated the expression of PCNA, Cyclin D1, Vimentin, MMP2 and MMP9 compared to that in the control group. Interestingly, an Erk1/2 inhibitor reversed the expression of the above proteins. CONCLUSION: Our data suggest that MSC-Exo can inhibit neointimal hyperplasia after carotid artery injury by accelerating re-endothelialization, which is accompanied by activation of the Erk1/2 signalling pathway. Importantly, our study provides a novel cell-free approach for the treatment of restenosis diseases after intervention.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões das Artérias Carótidas / Exossomos / Células-Tronco Mesenquimais Limite: Animals / Humans Idioma: En Revista: Stem Cell Res Ther Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões das Artérias Carótidas / Exossomos / Células-Tronco Mesenquimais Limite: Animals / Humans Idioma: En Revista: Stem Cell Res Ther Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China