Effect of Human Umbilical Cord-derived Mesenchymal Stem Cells on Murine Model of Bronchiolitis Obliterans Like Injury.

2020 
BACKGROUND Bronchiolitis obliterans (BO) is a fatal respiratory disease characterized by obliteration of small airways. Mesenchymal stem cells (MSCs) is a promising candidate for cell-based therapy. OBJECTIVE To evaluated the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on murine model of bronchiolitis obliterans like injury (BOLI). METHOD The murine model of BOLI was established by administrating of diacetyl (DA) via intratracheal instillation. Treatment of HUC-MSCs or HUC-MSCs culture medium (HUC-MSCs-CM) were conducted in BOLI model. RESULTS The pathogenic manifestations, lung function and number of neutrophils were similar between oropharyngeal inhalation DA group (OPI-DA), intratracheal instillation group (ITI-DA), however, the less reduction of weight and higher survival rate were observed in ITI-DA groups. Compared with the control groups, the trend of weight loss was significantly reduced (P<0.05), and the pulmonary function was significantly improved (P<0.05) in HUC-MSCs and HUC-MSCs-CM groups. Masson staining and HE staining showed that the deposition of collagen around bronchioles and blood vessels is less and airway epithelial cells and basal cells in lung tissue repaired better in HUC-MSCs and HUC-MSCs-CM groups compared with the control groups. Immunofluorescence shows the expression of E-cadherin and CK-5 were significantly higher in HUC-MSCs and HUC-MSCs-CM groups compared with control groups, while HUC-MSCs themselves did not express E-cadherin or CK-5. The Dil label showed HUC-MSCs gradually reduced after 2 days in bronchus and 4 days in bronchiole. CONCLUSION HUC-MSCs could help to repair airway epithelial cells in a murine model of BOLI. It might be related with paracrine factors of HUC-MSCs. This article is protected by copyright. All rights reserved.
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