Chen X.-YChen Y.-YLin WChen C.-HWen Y.-CHsiao T.-CChou H.-CChung K.FChuang H.-C.TA-CHIH HSIAO2022-03-222022-03-2220212296858Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85116884636&doi=10.3389%2ffmed.2021.713824&partnerID=40&md5=bff9c679638865b8db8efcb9595026c9https://scholars.lib.ntu.edu.tw/handle/123456789/598657Human 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.cigarette smokeCOPDemphysemainflammationstem cellCXCL1 chemokineelastinfibronectininterleukin 17interleukin 1betakeratinocyte derived chemokinemacrophage elastasemessenger RNAtumor necrosis factoranimal experimentanimal modelanimal tissueantiinflammatory activityArticlebody weightbronchoalveolar lavage fluidC57BL 6 mousecell proliferationcell viabilitychronic obstructive lung diseasecontrolled studycytokine productiondisease severityhumanhuman celllung emphysemalung fibroblastlung infiltratelymphocyte countmalemousemRNA expression levelnonhumanprotein blood leveltreatment outcomeumbilical cord mesenchymal stem cell transplantation[SDGs]SDG3journal article10.3389/fmed.2021.7138242-s2.0-85116884636