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

Xiao-Yue Chen,Hsiao-Chi Chuang,Hsiu-Chu Chou,Yu-Chieh Wen,Willie Lin,Ta-Chih Hsiao,Kian Fan Chung,Yi-Ying Chen,Chien-Han Chen

doi:10.3389/fmed.2021.713824

Abstract

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.

Highlights

Chronic obstructive pulmonary disease (COPD) is currently one of the world’s highest causes of mortality and ranks fifth worldwide in terms of disease burden [1,2,3]
We observed that hUC-MSCs decreased the emphysema severity and reduced lung and systemic inflammatory infiltration in mice with cigarette smoke (CS)-induced emphysema
We observed that hUC-MSCs increased the proliferation of lung fibroblasts after CS extract (CSE) exposure. hUC-MSCs may ameliorate emphysematous lung lesions in chronic obstructive pulmonary disease (COPD)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is currently one of the world’s highest causes of mortality and ranks fifth worldwide in terms of disease burden [1,2,3]. About 80–90% of COPD patients are related to cigarette smoking [4]. A previous study found that exposure to cigarette smoke (CS) for 12 weeks induced emphysematous lung lesions in rats [5]. This irreversible alveolar destruction and emphysematous changes due to CS exposure resulted in higher mortality and difficulties in treating COPD. Recent studies demonstrated immunoregulatory functions of MSCs in treating graft vs host disease [7, 8]. Recruitment of MSCs to the lungs provides new insights that MSCs may have greater paracrine effects in the lungs. The effects of MSCs on lung disease treatment were recently noted [12, 13]

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Methods

Conclusion