Therapeutic Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Recovering From Murine Pulmonary Emphysema Under Cigarette Smoke Exposure

Frontiers in Medicine

Hsiu-Chu Chou¹  Ta-Chih Hsiao²  Xiao-Yue Chen³  Chien-Han Chen⁴  Willie Lin⁴  Yu-Chieh Wen⁴  Kian Fan Chung⁵  Yi-Ying Chen⁶  Hsiao-Chi Chuang⁷ 

[1] Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Environmental Engineering, National Taiwan University, Taipei, Taiwan;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;Meridigen Biotech Co., Ltd., Taipei, Taiwan;National Heart and Lung Institute, Imperial College London, London, United Kingdom;School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan;School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan;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;

关键词: cigarette smoke;    COPD;    emphysema;    inflammation;    stem cell;   

DOI  :  10.3389/fmed.2021.713824

来源: Frontiers

【 摘 要 】

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were shown to have potential for immunoregulation and tissue repair. The objective of this study was to investigate the effects of hUC-MSCs on emphysema in chronic obstructive pulmonary disease (COPD). The C57BL/6JNarl mice were exposed to cigarette smoke (CS) for 4 months followed by administration of hUC-MSCs at 3 × 106 (low dose), 1 × 107 (medium dose), and 3 × 107 cells/kg body weight (high dose). The hUC-MSCs caused significant decreases in emphysema severity by measuring the mean linear intercept (MLI) and destructive index (DI). A decrease in neutrophils (%) and an increase in lymphocytes (%) in bronchoalveolar lavage fluid (BALF) were observed in emphysematous mice after hUC-MSC treatment. Lung levels of interleukin (IL)-1β, C-X-C motif chemokine ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and matrix metalloproteinase (MMP)-12 significantly decreased after hUC-MSC administration. Significant reductions in tumor necrosis factor (TNF)-α, IL-1β, and IL-17A in serum occurred after hUC-MSC administration. Notably, the cell viability of lung fibroblasts improved with hUC-MSCs after being treated with CS extract (CSE). Furthermore, the hUC-MSCs-conditioned medium (hUC-MSCs-CM) restored the contractile force, and increased messenger RNA expressions of elastin and fibronectin by lung fibroblasts. In conclusion, hUC-MSCs reduced inflammatory responses and emphysema severity in CS-induced emphysematous mice.

【 授权许可】

CC BY