Article ; Online: A Tumor Necrosis Factor-α and Hypoxia-Induced Secretome Therapy for Myocardial Repair.
The Annals of thoracic surgery
2017 Volume 105, Issue 3, Page(s) 715–723
Abstract: Background: Poor viability and retention of transplanted bone marrow mesenchymal stem cells (BM-MSC) remains an obstacle in promoting healing after myocardial infarction (MI). This study aimed to understand the migratory, angiogenic, and ... ...
Abstract | Background: Poor viability and retention of transplanted bone marrow mesenchymal stem cells (BM-MSC) remains an obstacle in promoting healing after myocardial infarction (MI). This study aimed to understand the migratory, angiogenic, and cardioprotective effects induced by tumor necrosis factor (TNF)-α and hypoxia through rat BM-MSC (rBM-MSC) paracrine secretions, collectively referred to as secretome, after MI. Methods: Secretome from rBM-MSC cultures treated with various combinations of H9c2 cardiomyoblast-conditioned medium, TNF-α, and hypoxia was initially collected. Immunocytochemistry, Western blot analyses, and transwell cell migration assays were conducted. In vivo, echocardiography was performed on rats with induced MI after their treatment with TNF-α and hypoxia-induced secretome. Results: Immunocytochemistry confirmed the presence of TNF receptors 1 and 2 on rBM-MSCs. Western blot analyses of rBM-MSCs treated with TNF-α and hypoxia showed an overall increasing trend in the expression of antiinflammatory proteins and angiogenic and migratory cytokines (transforming growth factor-β, fibroblast growth factor-2, angiopoietin-2, vascular endothelial growth factor-1). In addition, the TNF-α and hypoxia-induced secretome significantly increased the in vitro rBM-MSCs migration. In the rat MI model, the rats treated with the TNF-α and hypoxia-induced secretome had a significantly higher left ventricular fractional shortening than the control group. Conclusions: Our data suggest that after MI, rBM-MSCs secrete paracrine factors in response to TNF-α and hypoxia that work together to manipulate the microenvironment and decrease inflammation. In addition, these signaling factors trigger angiogenic and migratory effects at the site of the infarct to promote myocardial healing and improve the cardiac function. |
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MeSH term(s) | Animals ; Cell Culture Techniques ; Cell Hypoxia ; Culture Media, Conditioned ; Disease Models, Animal ; Intercellular Signaling Peptides and Proteins/metabolism ; Intercellular Signaling Peptides and Proteins/therapeutic use ; Mesenchymal Stem Cells/metabolism ; Myocardial Infarction/therapy ; Rats ; Rats, Inbred Lew ; Tumor Necrosis Factor-alpha/therapeutic use |
Chemical Substances | Culture Media, Conditioned ; Intercellular Signaling Peptides and Proteins ; Tumor Necrosis Factor-alpha |
Language | English |
Publishing date | 2017-12-16 |
Publishing country | Netherlands |
Document type | Journal Article |
ZDB-ID | 211007-6 |
ISSN | 1552-6259 ; 0003-4975 |
ISSN (online) | 1552-6259 |
ISSN | 0003-4975 |
DOI | 10.1016/j.athoracsur.2017.09.005 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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