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  3. YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

  • Biomed Pharmacother. 2023 Jan 25;159:114302. doi: 10.1016/j.biopha.2023.114302.
Xiao-Yue Chen 1,  Kuan-Yuan Chen 2,  Po-Hao Feng 3,  Kang-Yun Lee 4,  Yu-Ting Fang 5,  You-Yin Chen 6,  Yu-Chun Lo 7,  Pankaj K Bhavsar 8,  Kian Fan Chung 9,  Hsiao-Chi Chuang 10
Affiliations

Affiliations

  • 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: iryuoscar@gmail.com.
  • 2 Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Electronic address: 14388@s.tmu.edu.tw.
  • 3 Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: fengpohao@tmu.edu.tw.
  • 4 Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: leekangyun@tmu.edu.tw.
  • 5 Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: crosshine@fda.gov.tw.
  • 6 Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan; The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Industrial Ph.D. Program of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: youyin.chen@gmail.com.
  • 7 The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: aricalo@tmu.edu.tw.
  • 8 National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: p.bhavsar@imperial.ac.uk.
  • 9 National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: f.chung@imperial.ac.uk.
  • 10 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; National Heart and Lung Institute, Imperial College London, London, UK; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: chuanghc@tmu.edu.tw.
PMID: 36701989 DOI: 10.1016/j.biopha.2023.114302
Abstract

Acute respiratory distress syndrome (ARDS) contributes to higher mortality worldwide. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have immunomodulatory and regenerative potential. However, the effects of hUC-MSCs as an ARDS treatment remain unclear. We investigated the role of hUC-MSCs in the differentiation of type II alveolar epithelial cells (AECII) by regulating Yes-associated protein (YAP) in ARDS. Male C57BL/6JNarl mice were intratracheally (i.t.) administered lipopolysaccharide (LPS) to induce an ARDS model, followed by a single intravenous (i.v.) dose of hUC-MSCs. hUC-MSCs improved pulmonary function, decreased inflammation on day 3, and mitigated lung injury by reducing the lung injury score and increasing lung aeration (%) in mice on day 7 (p < 0.05). hUC-MSCs inactivated YAP on AECII and facilitated cell differentiation by decreasing Pro-surfactant protein C (Pro-SPC) and Galectin 3 (LGALS3) while increasing podoplanin (T1α) in lungs of mice (p < 0.05). In AECII MLE-12 cells, both coculture with hUC-MSCs after LPS exposure and the YAP Inhibitor, verteporfin, reduced Pro-SPC and LGALS3, whereas the YAP Inhibitor increased T1α expression (p < 0.05). In conclusion, hUC-MSCs ameliorated lung injury of ARDS and regulated YAP to facilitate AECII differentiation.

Keywords

Alveoli; Inflammation; Pneumocytes; Regeneration; Stem cells.

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