Effect of human umbilical cord-derived mesenchymal stem cells on murine model of bronchiolitis obliterans like injury

Pediatr Pulmonol. 2021 Jan;56(1):129-137. doi: 10.1002/ppul.25128. Epub 2020 Oct 29.

Abstract

Background: Bronchiolitis obliterans is a fatal respiratory disease characterized by the obliteration of small airways. Mesenchymal stem cells (MSCs) is a promising candidate for cell-based therapy.

Objective: To evaluate the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on a 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) was conducted in the BOLI model.

Results: The pathogenic manifestations, lung function, and the number of neutrophils were similar between the oropharyngeal inhalation DA group (OPI-DA), intratracheal instillation group (ITI-DA); however, 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 < .05), and the pulmonary function was significantly improved (p < .05) in HUC-MSCs and HUC-MSCs-CM groups. Masson staining and hematoxylin and eosin 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 cytokeratin 5 (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 DiI label showed HUC-MSCs gradually reduced after 2 days in the 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 to paracrine factors of HUC-MSCs.

Keywords: HUC-MSCs; HUC-MSCs-CM; airway epithelial cells; bronchiolitis obliterans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchiolitis Obliterans*
  • Cell Count
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Disease Models, Animal*
  • Epithelial Cells
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Umbilical Cord / cytology