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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium, via the TGF-β1/Smad3 pathway

  • Kim, Ran (Department of Biology Education, College of Education, Pusan National University) ;
  • Song, Byeong-Wook (Department of Medical Science, College of Medicine, Catholic Kwandong University) ;
  • Kim, Minji (Department of Biology Education, College of Education, Pusan National University) ;
  • Kim, Won Jung (Department of Biology Education, College of Education, Pusan National University) ;
  • Lee, Hee Won (Department of Biology Education, College of Education, Pusan National University) ;
  • Lee, Min Young (Department of Molecular Physiology, College of Pharmacy, Kyungpook National University) ;
  • Kim, Jongmin (Department of Life Systems, Sookmyung Women's University) ;
  • Chang, Woochul (Department of Biology Education, College of Education, Pusan National University)
  • Received : 2020.08.26
  • Accepted : 2020.10.05
  • Published : 2020.11.30
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Abstract

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

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References

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