Adipose-derived mesenchymal stem cells suppress ozone-mediated airway inflammation in a mouse model of chronic obstructive pulmonary disease

Mol Immunol. 2022 Nov:151:95-102. doi: 10.1016/j.molimm.2022.08.020. Epub 2022 Sep 13.

Abstract

Objective and design: Ozone exposure is an important risk factor for Chronic Obstructive Pulmonary Disease (COPD) which is a global public health concern. Until now, there is no effective approach to reverse airflow limitation and accelerated loss of lung function completely. Here, we delineate the efficacy of mouse allogeneic adipose-derived mesenchymal stem cells (mASCs) in the treatment of COPD mice by intratracheal and intravenous administration.

Methods: In this study, we established ozone-exposed COPD model in mice and were administered intratracheally or intravenously with mASCs which were extracted, cultured, and identified in vitro.

Results: We observed that exposure to ozone resulted in a marked lung neutrophilia with high levels of inflammatory cell counts, enhanced expression of cytokines IL-1β and TNF-α, reduced expression of IL-10, lung function and airspace enlargement. mASCs intratracheal administration rescured the lung neutrophilia, lung function and emphysema-like phenotype. Similar results were observed in mice with mASCs intravenous administration. But the altered levels of serum cytokines in mice with mASCs intratracheal administration appears more robust than those in mice with mASCs intravenous administration.

Conclusions: Collectively, these data indicate that intratracheal administration of mASCs appears more effective in treating ozone-induced COPD compared to intravenous administration of mASCs, although the two approaches can be comparable in safety. mASCs are expected to become a new potential intervention strategy for COPD.

Keywords: Adipose-derived mesenchymal stem cells; Airway inflammation; Chronic obstructive pulmonary disease; Emphysema; Ozone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation / metabolism
  • Interleukin-10 / metabolism
  • Lung / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Ozone*
  • Pulmonary Disease, Chronic Obstructive* / chemically induced
  • Pulmonary Disease, Chronic Obstructive* / therapy
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Ozone