Therapeutic Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Recovering From Murine Pulmonary Emphysema Under Cigarette Smoke Exposure
Journal
Frontiers in Medicine
Journal Volume
8
Date Issued
2021
Author(s)
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. ? Copyright ? 2021 Chen, Chen, Lin, Chen, Wen, Hsiao, Chou, Chung and Chuang.
Subjects
cigarette smoke
COPD
emphysema
inflammation
stem cell
CXCL1 chemokine
elastin
fibronectin
interleukin 17
interleukin 1beta
keratinocyte derived chemokine
macrophage elastase
messenger RNA
tumor necrosis factor
animal experiment
animal model
animal tissue
antiinflammatory activity
Article
body weight
bronchoalveolar lavage fluid
C57BL 6 mouse
cell proliferation
cell viability
chronic obstructive lung disease
controlled study
cytokine production
disease severity
human
human cell
lung emphysema
lung fibroblast
lung infiltrate
lymphocyte count
male
mouse
mRNA expression level
nonhuman
protein blood level
treatment outcome
umbilical cord mesenchymal stem cell transplantation
SDGs
Type
journal article