Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair

Stem Cell Rev Rep. 2019 Feb;15(1):112-125. doi: 10.1007/s12015-018-9844-7.

Abstract

Background: The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model.

Methods: Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48 h after injury. The post mortem was performed 3 days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments.

Result(s): Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p < 0.001), as reflected by improved of structural changes such as thickness of the basement membrane, epithelium, mucosa and sub-mucosa regions. The airway inflammation score of both treatment groups revealed a significant reduction of inflammation and granulocyte infiltration at the peribronchiale and perivascular regions (p < 0.05). Administration of aerosolised MSCs alone was resulted in significant reduction in the levels of pro-inflammatory genes (IL-4 and TGF-β) while treatment with aerosolised MSC-pANGPT1 led to further reduction of various pro-inflammatory genes to the base-line values (IL4, TNF, MMP9 and TGF-β). Treatment with both aerosolised MSCs and MSC-pANGPT1 cells was also alleviated the number of airway inflammatory cells in the bronchoalveolar lavage (BAL) fluid and goblet cell hyperplasia.

Conclusion(s): Our findings suggest that treatment with MSCs alone attenuated airway inflammation and structural changes of the airway. Treatment with MSC-pANGPT1 provided an additional effect in reducing the expression levels of various pro-inflammatory genes. Both of these treatment enhancing airway repair and therefore may provide a basis for the development of an innovative approach for the treatment and prevention of airway inflammatory diseases.

Keywords: Aerosol delivery; Airway inflammation; Angiopoietin-1; Mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols / administration & dosage*
  • Angiopoietin-1 / metabolism*
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Shape
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Goblet Cells / metabolism
  • Goblet Cells / pathology
  • Granulocytes / pathology
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Lung / pathology*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Ovalbumin
  • Rabbits
  • Wound Healing*

Substances

  • Aerosols
  • Angiopoietin-1
  • Ovalbumin