Effects of bone marrow mesenchymal stem cells on CD4+CD25+ regulatory T cells and airway inflammation in asthmatic mice

Background: Decreased function and reduced number of CD4+CD25+ regulatory T cells have been considered the major manifestation of immunity dysfunction in asthma patients. Mesenchymal stem cells (MSCs) have effects of immunoregulation, which can up-regulate CD4+CD25+ regulatory T cells, inhibit proliferation of lymphocytes, and have been widely used in many immune diseases. Objective: To study the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on the CD4+CD25+ regulatory T cells of peripheral blood and the airway inflammation in asthmatic mice. Design, time and setting: The randomized controlled animal experiment was performed at the Central Laboratory, Second Affiliated Hospital, Sun Yat-sen University from September 2006 to May 2008. Materials: Thirty-four SPF BALB/c mice were selected for this study. Of them, 4 male mice aged 3-4 weeks were used for preparing BMSCs. Thirty female mice aged six weeks were equally and randomly divided into normal control, model control and cell transplantation groups. Methods: Mice in the model control and cell transplantation groups were sensitized with 0.2 mL 500 mg/L ovalbumin (OVA) by a combination of intraperitoneal injection and repeated 50 g/L OVA solution challenges to establish the mouse asthma model. In the normal control group, normal saline of the equal volume was given instead of OVA. Mice in the cell transplantation group were intravenously administered MSCs at 10 days after sensitization. Main outcomes measures: The number of CD4+CD25+ regulatory T cells in peripheral blood was detected by flow cytometry. The total cell number of bronchoalveolar lavage fluid, the number of eosinophils, lymphocytes and neutrophils were counted to analyze the degree of inflammation of the airway together with pathological section. Results: Compared to the normal control group, the number of CD4+CD25+ regulatory T cells in peripheral blood was significantly decreased in the model control group (t=7.742, P < 0.05). Compared to the model control group, the number of CD4+CD25+ regulatory T cells in peripheral blood was significantly increased in the cell transplantation group (t=7.455, P < 0.05). There were significantly differences in the total cell number of bronchoalveolar lavage fluid, the number of eosinophils, lymphocytes and neutrophils (P < 0.05). The total cell number of bronchoalveolar lavage fluid was higher in the model control group compared with the normal control group (P < 0.05). The total cell number of bronchoalveolar lavage fluid was lower in the cell transplantation group compared to the model control group (P < 0.05). There was no obvious infiltration of inflammatory cells in the airways in the normal control group. However, there were a great number of inflammatory cells, epithelial proliferation, partial breakage and defluvium of the airway epithelium in the bronchus, below the vessel mucous membrane and around lung tissues in the model control group. Airway inflammation was significantly relieved in the cell transplantation group. Conclusions: MSCs via intravenous infusion can up-regulate CD4+CD25+ regulatory T cells of peripheral blood in asthmatic mice and relieve the inflammation of the lung in asthmatic mice.