Effect Of Adipose Derived Mesenchymal Stem Cells In A Mouse Model Of Ozone-induced Chronic Obstructive Pulmonary Disease

Background and ObjectiveChronic obstructive pulmonary disease(COPD)is a common disease which is seriously harmful to human health and affects the quality of life of the patients.Air pollution is an important risk factor for COPD,and ozone is one of the most common air pollution.Mesenchymal stem cells(MSCs)are pluripotent stem cells originated from early mesoderm development and have self-renewal capacity and multi-directional differentiation,can play a role in immune regulation tissue regeneration and repair effect from a variety of ways.This study was designed to establish the ozone induced COPD model,and to study the safety and efficacy of two kinds of adipose derived mesenchymal stem cells in the treatment of COPD mice by systemic and local transplantation.MethodsIn this study,the COPD model was established by ozone exposure in mice.The mouse allogeneic adipose derived mesenchymal stem cells(m ASCs)and human adipose derived mesenchymal stem cells(h ASCs)were isolated,cultured and identified in vitro.m ASCs and h ASCs were transplanted intravenously/intratracheally to COPD mice to investigate the therapeutic effect on airway evaluate the safety and efficacy in the treatment in terms of lung function,alveolar lavage cell count,lung tissue pathology and expression of cytokines IL-1,IL-10 and TNF-alpha.To compare the differences in the therapeutic effects of ASCs transplantation during the early stage of ozone exposure(3 weeks)and post modeling(6 weeks)on COPD mice.ResultsOzone exposure can establish COPD mice model which is characterized by pulmonary emphysema and airway inflammation.The transplantation of m ASCs and h ASCs by two approaches were both safe in the observation period,can improve pulmonary function and reduce the number of inflammatory cells in bronchoalveolar lavage fluid(BALF)and alleviate the degree of emphysema.The levels of IL-1?and TNF-? in serum and BALF were decreased and the level of IL-10 were increased in different degrees.Compared with two kinds of transplantation methods,local therapy had more significant effects in.in improving the degree of emphysema and decreasing the percentage of BALF neutrophil.Early transplantation and late transplantation in the process of ozone exposure both had therapeutic effects on COPD,and the difference was not significant.ConclusionsIntravenous and intratracheal transplantation of allogeneic and xenogeneic adipose derived mesenchymal stem cells can be safe and effective in the treatment of ozone-induced mice chronic obstructive lung disease.The mechanism of improvement in lung function,emphysema,airway inflammation remains to be further study.Adipose-derived mesenchymal stem cells are expected to become a new therapeutic means in the treatments of chronic obstructive pulmonary disease.