The investigation of therapeutic potential of boron derivatives and mesenchymal stem cell lysate on house dust mite-induced asthma in mice

Asthma is a respiratory disease and affects more than 350 million people worldwide, especially in developed countries. It is characterized with airway hyperresponsiveness (AHR), airway inflammation and remodeling. Asthma brings a serious economic burden on countries because of the high treatment costs and loss of labor. Approximately 50-70 percent of asthma patients have a T helper 2 (Th2) immunity which is characterized by type 2 inflammation. Allergic asthma is associated with sensitization to allergen such as pollen, house dust mite (HDM), and pets. Different treatment methods are used to reduce or control the symptoms, but no definitive treatment for asthma has been found, yet. Some of these treatments are corticosteroids, beta-2 agonist drugs, omalizumab which is anti-IgE based therapy, anti-IL-5 based therapy with mepolizuman, reslizumab and benralizumab, and mesenchymal stem cell (MSC)-based immune modulation. However, definitive treatment is needed. In this thesis, the therapeutic effects of boron derivatives such as sodium pentaborate pentahydrate (SPP), sodium perborate tetrahydrate (SPT), and MSC lysate on HDM-induced allergic asthma model were investigated. To determine the therapeutic effects of these agents on 6-8 weeks female BALB/c mice, these agents were delivered on day 12 and 14 intranasally ensuing initiation and sensitization phase using 50 g/day HDM during the first four days. A challenge phase was initiated by the re-administration of HDM between days 15-18 days. Lung and the mediastinal lymph node (mLN) were harvested and blood samples were collected from all experimental groups on day 19. Lung histopathology, serum IgE levels and immune cell numbers and percentages of total dendritic cells (DC), CD11b+ DCs, CD103+ DCs, alveolar macrophages, T lymphocytes, and neutrophils were determined using hematoxylin eosin staining, ELISA, flow cytometry, respectively. We found that SPP has a therapeutic potential for asthma treatment. It decreased the number of lung infiltrating immune cells and serum IgE levels. However, neither SPT nor MSC lysate introduced any changes on the pathology or immunology of asthma in a therapeutical sense. In a conclusion, we showed for first time in the literature, intranasal delivery of SPP has a therapeutic potential of asthma.