Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Adjuvant role of macrophages in stem cell-induced cardiac repair in rats

  • Lim, Soo yeon (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Cho, Dong Im (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Jeong, Hye-yun (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Kang, Hye-jin (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Kim, Mi Ra (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Cho, Meeyoung (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Kim, Yong Sook (Cell Regeneration Research Center, Chonnam National University Hospital) ;
  • Ahn, Youngkeun (Cell Regeneration Research Center, Chonnam National University Hospital)
  • Received : 2018.04.06
  • Accepted : 2018.07.18
  • Published : 2018.11.30
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Abstract

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

Keywords

Acknowledgement

Supported by : National Research Foundation (NRF) of Korea, Chonnam National University Hospital Biomedical Research Institute

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