Abstract
Objective Through orthotopic tracheal transplantation model to analyze the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) on obliterative bronchiolitis (OB). Methods Brown Norway-to-Lewis rats were subjected to orthotopic tracheal transplantation, and intragastically given 15 mg/(kg·d) cyclosporine (CsA) until the day when the animals were ready to be killed. BMSCs single cell suspension liquid [1 ml, (1×106/ml) and normal saline (NS) (1 ml) were injected via the tail vein, respectively. Tracheal grafts were harvested at 7th, 30th, and 60th days post-transplantation. The tracheal luminal obliteration rate and epithelial loss were assessed on sections stained with hematoxylin and eosin. CD4+ and CD8+ T lymphocytes in peripheral blood were aexamined using flow cytometry. The expression of transforming factor-beta1 (TGF-β1) was detected by Western blotting. Results The luminal obliteration in NS, CsA and BMSCs treated groups after 60 days post-transplant were (52.62±10.21)%, (28.52±8.81)% and (21.30±2.27)% respectively, CsA and BMSCs were significantly attenuated (P=0.030, P=0.004); the epithelial loss were (96.10±0.86)%, (93.67±4.04)% and (25.26±1.10)% respectively, BMSCs were protective against the epithelial loss post-transplant compared with NS and CsA group (P=0.009); the percentage of CD8+ T lymphocyte in peripheral blood were (24.13±1.82)%, (49.50±3.03)% and (26.27±0.40)% respectively, which were significantly suppressed by BMSCs compared with NS and CsA group (P=0.007). The relative expression quantity of TGF-β1 were 1.21, 0.77 and 0.36 respectively, which can decrease TGF-β1 expression induced by transplant (P=0.000). Conclusion BMSCs could prevent development of airway occlusion through downregulating the expression of TGF-β1, reducing the CD8+ T lymphocyte infiltration and enhancing epithelial preservation in a orthotopic tracheal transplantation mouse model of OB. Key words: Orthotopic tracheal transplantation; Bone marrow mesenchymal stem cells; Cyclosporine; Lung transplantation; Obliterative bronchiolitis; Rat
Published Version
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