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Kang K, Ma R, Cai W, et al. Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction. Stem Cells Int. 2015;2015:659890doi: 10.1155/2015/659890.
Kang, K., Ma, R., Cai, W., Huang, W., Paul, C., Liang, J., Wang, Y., Zhao, T., Kim, H. W., Xu, M., Millard, R. W., Wen, Z., & Wang, Y. (2015). Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction. Stem cells international, 2015659890. https://doi.org/10.1155/2015/659890
Kang, Kai, et al. "Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction." Stem cells international vol. 2015 (2015): 659890. doi: https://doi.org/10.1155/2015/659890
Kang K, Ma R, Cai W, Huang W, Paul C, Liang J, Wang Y, Zhao T, Kim HW, Xu M, Millard RW, Wen Z, Wang Y. Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction. Stem Cells Int. 2015;2015:659890. doi: 10.1155/2015/659890. Epub 2015 May 05. PMID: 26074976; PMCID: PMC4436515.
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Stem Cells Int. 2015;2015:659890. doi: 10.1155/2015/659890. Epub 2015 May 05.

Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction.

Stem cells international

Kai Kang, Ruilian Ma, Wenfeng Cai, Wei Huang, Christian Paul, Jialiang Liang, Yuhua Wang, Tiejun Zhao, Ha Won Kim, Meifeng Xu, Ronald W Millard, Zhili Wen, Yigang Wang

Affiliations

  1. Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
  2. Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA ; Department of Cardiology, The People's Hospital of Sanya, Sanya, Hainan 572000, China.
  3. Department of Urinary Surgery, Xining City Hospital, Qinghai 810000, China.
  4. Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
  5. Infection Hospital of Nanchang University, Nanchang, Jiangxi 330002, China.

PMID: 26074976 PMCID: PMC4436515 DOI: 10.1155/2015/659890

Abstract

Background and Objective. Exosomes secreted from mesenchymal stem cells (MSC) have demonstrated cardioprotective effects. This study examined the role of exosomes derived from MSC overexpressing CXCR4 for recovery of cardiac functions after myocardial infarction (MI). Methods. In vitro, exosomes from MSC transduced with lentiviral CXCR4 (Exo(CR4)) encoding a silencing sequence or null vector were isolated and characterized by transmission electron microscopy and dynamic light scattering. Gene expression was then analyzed by qPCR and Western blotting. Cytoprotective effects on cardiomyocytes were evaluated and effects of exosomes on angiogenesis analyzed. In vivo, an exosome-pretreated MSC-sheet was implanted into a region of scarred myocardium in a rat MI model. Angiogenesis, infarct size, and cardiac functions were then analyzed. Results. In vitro, Exo(CR4) significantly upregulated IGF-1α and pAkt levels and downregulated active caspase 3 level in cardiomyocytes. Exo(CR4) also enhanced VEGF expression and vessel formation. However, effects of Exo(CR4) were abolished by an Akt inhibitor or CXCR4 knockdown. In vivo, Exo(CR4) treated MSC-sheet implantation promoted cardiac functional restoration by increasing angiogenesis, reducing infarct size, and improving cardiac remodeling. Conclusions. This study reveals a novel role of exosomes derived from MSC(CR4) and highlights a new mechanism of intercellular mediation of stem cells for MI treatment.

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