Bone Marrow Mesenchymal Stem Cell with Up-Regulation of MicroRNA-206 in the Treatment of Bronchopulmonary Dysplasia in Newborn Mice

Abstract

Background:: Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm neonates with a few therapeutic options. Our previous studies suggested that bone marrow-derived mesenchymal stem cell (BMSC) therapy is effective in the treatment of BPD in mouse models. Furthermore, microRNA-206 (miR-206) suggested having a correlation with BPD by regulating the expression of fibronectin 1 (FN1). Objectives:: The aim of this study was to characterize the role of BMSCs with the up-regulation of miR-206 in the treatment of BPD in newborn mice. Methods: The BPD mouse model was induced by 60% oxygen. BMSCs transfected with miR-206 or negative control (NC) plasmid were administered on postnatal day 7 (P7) and every following week through an intraperitoneal injection (105 cells/animal) until P35. The mice were weighed and their lungs were weighed and prepared for histology. The expression levels of miR-206, FN1, and pulmonary surfactant-associated protein-C (SP-C) were determined through the quantitative polymerase chain reaction and under the immunofluorescence. The protein expression levels of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) were determined by ELISA. Results: BMSCs with up-regulation of miR-206 reduced the degrees of pulmonary edema, improved pulmonary architecture, and attenuated inflammation in BPD mice compared to the NC plasmid group. Furthermore, the up-regulation of miR-206 in BMSCs down-regulated the expression levels of TGF-β and IL-6 in plasma samples and of SP-C and FN1 in the lung tissue of BPD mice. Conclusions: BMSCs with up-regulation of miR-206 are effective in the treatment of BPD in newborn mice, and the study introduced a novel idea for the treatment of BPD.