International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Perivascular Stem Cells Suppress Inflammasome Activation during Inflammatory Responses in Macrophages

  • Kim, Jeeyoung (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Kim, Woo Jin (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Ha, Kwon-Soo (Scripps Korea Antibody Institute and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University) ;
  • Han, Eun-Taek (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Park, Won Sun (Department of Physiology, School of Medicine, Kangwon National University) ;
  • Yang, Se-Ran (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Hong, Seok-Ho (Department of Internal Medicine, School of Medicine, Kangwon National University)
  • Received : 2019.09.29
  • Accepted : 2019.10.10
  • Published : 2019.11.30
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Abstract

Background and Objectives: Perivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated. Methods and Results: In this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1β in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation. Conclusions: Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.

Keywords

Acknowledgement

This study was supported by grants from the Ministry of Science, ICT and Future Planning (2015R1A4A1038666), the National Research Foundation of Korea (NRF) funded by the Korean government (MIST) (2019R1A2C2005453) and the Global PhD Fellowship Program through the (NRF funded by the Ministry of Education (2018H1A2A1063441).

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