Mouse Bone Marrow Derived Mesenchymal Stem Cells Supress Airway Inflammation In Both Chronic and Acute Murine Asthma Model

RationaleThe aim of the present study was to investigate the efficacy of mouse compact bone (mCB) derived MSCs on lung histopathology and lymphocyte proliferation.MethodsmCB-MCS were isolated from BALB/c mice, characterized and marked by GFP. To generate murine models of chronic and acute asthma, mice were i.p. sensitized with OVA and exposed to aerolized OVA. mCB-MSCs (2.5x105 cells) were administrated i.v. after last nebulization. Mice were sacrified, and splenocytes and lung lymphocytes were isolated and marked with CFSE. Cells stimulated with OVA (40mg/ml) were cultured under suitable conditions for 5 days. Flow cytometric analysis and histopathological examination of lungs were evaluated. In histopathological analysis, the measurements were performed from minimum 5 points of each airway and mean values were calculated. Goblet cells stained with PAS enumarated in 1500 cells.ResultsIn sections stained with H&E, the distal [without MCS chronic:29,9mm acute:32,03mm; with MSC chronic:13,3mm acute:12,25mm] and proximal [without MCS chronic:42,6mm acute:28,97mm; with MSC chronic:17,4mm acute:18,9mm] airway epithelial thicknesses were observed to decrease in both mouse models. Likewise, in sections stained with PAS, a significant reduction in number of hyperplasic goblet cells in the proximal [without MSC chronic:140 acute:1200; with MSC chronic:4 acute:211] and distal [without MSC chronic:55 acute:118; with MSC chronic:0 acute:0] airways was observed. Morever, in the CFSE staining experiment, CB-MSCs inhibited lymphocyte proliferation in both asthma model.ConclusionsThe results reported here provide that mCB-MSCs may provide powerful alternative therapeutic for the treatment of chronic and acute asthma. This study was supported by TUBITAK-SBAG (110S368). RationaleThe aim of the present study was to investigate the efficacy of mouse compact bone (mCB) derived MSCs on lung histopathology and lymphocyte proliferation. The aim of the present study was to investigate the efficacy of mouse compact bone (mCB) derived MSCs on lung histopathology and lymphocyte proliferation. MethodsmCB-MCS were isolated from BALB/c mice, characterized and marked by GFP. To generate murine models of chronic and acute asthma, mice were i.p. sensitized with OVA and exposed to aerolized OVA. mCB-MSCs (2.5x105 cells) were administrated i.v. after last nebulization. Mice were sacrified, and splenocytes and lung lymphocytes were isolated and marked with CFSE. Cells stimulated with OVA (40mg/ml) were cultured under suitable conditions for 5 days. Flow cytometric analysis and histopathological examination of lungs were evaluated. In histopathological analysis, the measurements were performed from minimum 5 points of each airway and mean values were calculated. Goblet cells stained with PAS enumarated in 1500 cells. mCB-MCS were isolated from BALB/c mice, characterized and marked by GFP. To generate murine models of chronic and acute asthma, mice were i.p. sensitized with OVA and exposed to aerolized OVA. mCB-MSCs (2.5x105 cells) were administrated i.v. after last nebulization. Mice were sacrified, and splenocytes and lung lymphocytes were isolated and marked with CFSE. Cells stimulated with OVA (40mg/ml) were cultured under suitable conditions for 5 days. Flow cytometric analysis and histopathological examination of lungs were evaluated. In histopathological analysis, the measurements were performed from minimum 5 points of each airway and mean values were calculated. Goblet cells stained with PAS enumarated in 1500 cells. ResultsIn sections stained with H&E, the distal [without MCS chronic:29,9mm acute:32,03mm; with MSC chronic:13,3mm acute:12,25mm] and proximal [without MCS chronic:42,6mm acute:28,97mm; with MSC chronic:17,4mm acute:18,9mm] airway epithelial thicknesses were observed to decrease in both mouse models. Likewise, in sections stained with PAS, a significant reduction in number of hyperplasic goblet cells in the proximal [without MSC chronic:140 acute:1200; with MSC chronic:4 acute:211] and distal [without MSC chronic:55 acute:118; with MSC chronic:0 acute:0] airways was observed. Morever, in the CFSE staining experiment, CB-MSCs inhibited lymphocyte proliferation in both asthma model. In sections stained with H&E, the distal [without MCS chronic:29,9mm acute:32,03mm; with MSC chronic:13,3mm acute:12,25mm] and proximal [without MCS chronic:42,6mm acute:28,97mm; with MSC chronic:17,4mm acute:18,9mm] airway epithelial thicknesses were observed to decrease in both mouse models. Likewise, in sections stained with PAS, a significant reduction in number of hyperplasic goblet cells in the proximal [without MSC chronic:140 acute:1200; with MSC chronic:4 acute:211] and distal [without MSC chronic:55 acute:118; with MSC chronic:0 acute:0] airways was observed. Morever, in the CFSE staining experiment, CB-MSCs inhibited lymphocyte proliferation in both asthma model. ConclusionsThe results reported here provide that mCB-MSCs may provide powerful alternative therapeutic for the treatment of chronic and acute asthma. This study was supported by TUBITAK-SBAG (110S368). The results reported here provide that mCB-MSCs may provide powerful alternative therapeutic for the treatment of chronic and acute asthma. This study was supported by TUBITAK-SBAG (110S368).