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Effectiveness of Exosome Mediated Mir-126 and Mir-146A Delivery on Cardiac Tissue Regeneration Publisher Pubmed



Shafei S1 ; Khanmohammadi M2 ; Ghanbari H3 ; Nooshabadi VT4 ; Tafti SHA5 ; Rabbani S5 ; Kasaiyan M6 ; Basiri M7 ; Tavoosidana G1, 8
Authors
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Authors Affiliations
  1. 1. Department of Molecular Medicine, School of Advanced Technologies in Medicine, International Campus Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Skull Base Research Center, School of Medicine, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
  3. 3. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
  5. 5. Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Clinical Research Development Unit of Farshchian Hospital, Hamedan University of Medical Sciences, Hamedan, Iran
  7. 7. Baim Institute for Clinical Research, Harvard Medical School, Boston, MA, United States
  8. 8. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Cell and Tissue Research Published:2022


Abstract

Despite advances in the treatment of acute myocardial infarction, due to the non-proliferative nature of adult cardiomyocytes, the injured myocardium is mainly replaced by fibrotic tissue, which ultimately causes heart failure. To prevent heart failure, particularly after myocardial infarction, exosome-based therapy has emerged as one of the most promising strategies to regenerate cardiac function. Exosomes can carry microRNAs in support of neovascularization, anti-inflammatory, and endogenous cardiac regeneration. This study demonstrated that animal rat models’ combination treatment with microRNA-126 and microRNA-146a mimics in exosomes is desirable for cardiac regeneration after myocardial infarction. The exosomes isolated from stem cells and loaded with microRNAs were characterized their impacts in cell migration, tube formation, and vascular endothelial growth factor degree. In the following, the usefulness of loaded microRNAs in exosomes and their encapsulation within alginate derivative hydrogel was analyzed in myocardial infarction for an animal model. Exosomes isolated and loaded with microRNAs showed the synergetic impact on cell migration, tube formation, and promoted vascular endothelial growth factor folding. Moreover, microRNAs loaded exosomes and encapsulated them in alginate hydrogel could help in reducing infarct size and improving angiogenesis in myocardial infarction. The angiogenesis markers including CD31 and connexion 43 upregulated for myocardial infarction models treated with alginate-based hydrogels loaded with exosomes and microRNAs-exosomes. Histological analysis indicated that myocardial infarction model rats treated with alginate hydrogel loaded with microRNAs-exosomes possessed lower and higher degrees of fibrosis and collagen fiber, respectively. These findings have important therapeutic implications for a myocardial infarction model through angiogenesis and vascular integrity regulation. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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