Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Intravenous Mesenchymal Stem Cell Administration Modulates Monocytes/Macrophages and Ameliorates Asthmatic Airway Inflammation in a Murine Asthma Model

  • Mo, Yosep (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Kang, Sung-Yoon (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Bang, Ji-Young (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Kim, Yujin (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Jeong, Jiung (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Jeong, Eui-Man (Department of Pharmacy, Jeju National University College of Pharmacy) ;
  • Kim, Hye Young (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Cho, Sang-Heon (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Kang, Hye-Ryun (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center)
  • Received : 2022.03.08
  • Accepted : 2022.07.07
  • Published : 2022.11.30
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Abstract

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. NRF-2017M3A9B4061887 and 2020R1A2C2007920). Parts of figures were created with BioRender.com.

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