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

Xiao-Yue Chen; Kuan-Yuan Chen; Po-Hao Feng; Kang-Yun Lee; Yu-Ting Fang; You-Yin Chen; Yu-Chun Lo; Pankaj K. Bhavsar; Kian Fan Chung; Hsiao-Chi Chuang

Biomedicine & Pharmacotherapy (Mar 2023)

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

Xiao-Yue Chen,
Kuan-Yuan Chen,
Po-Hao Feng,
Kang-Yun Lee,
Yu-Ting Fang,
You-Yin Chen,
Yu-Chun Lo,
Pankaj K. Bhavsar,
Kian Fan Chung,
Hsiao-Chi Chuang

Affiliations

Xiao-Yue Chen: 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
Kuan-Yuan Chen: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Po-Hao Feng: 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
Kang-Yun Lee: 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
Yu-Ting Fang: Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan
You-Yin Chen: 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
Yu-Chun Lo: The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Pankaj K. Bhavsar: National Heart and Lung Institute, Imperial College London, London, UK
Kian Fan Chung: National Heart and Lung Institute, Imperial College London, London, UK
Hsiao-Chi Chuang: 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; Correspondence to: Inhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.

Journal volume & issue: Vol. 159
p. 114302

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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