International Journal of Stem Cells

  • 제16권2호
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  • Pages.191-201
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  • 2023
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  • 2005-3606(pISSN)
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  • 2005-5447(eISSN)
한국줄기세포학회 (Korean Society for Stem Cell Research)
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Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

  • Youngheon Park (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Jimin Jang (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Jooyeon Lee (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Hyosin Baek (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Jaehyun Park (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Sang-Ryul Cha (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Se Bi Lee (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Sunghun Na (Department of Obstetrics and Gynecology, School of Medicine, Kangwon National University) ;
  • Jae-Woo Kwon (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Seok-Ho Hong (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Se-Ran Yang (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University)
  • 투고 : 2023.01.02
  • 심사 : 2023.02.06
  • 발행 : 2023.05.30
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초록

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.

키워드

과제정보

This work was supported by the National Research Foundation (NRF) funded by the Korean government (MSIT) (2020R1A2C2010712, 2020R1A5A8019180), the Korean Fund for Regenerative Medicine (KFRM) (22A0304L1-01).

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