Bone Marrow-derived Mesenchymal Stem Cells and Chronic Allograft Disease in a Bronchiolitis Obliterans Animal Model

Abstract

IntroductionBronchiolitis obliterans (BO) is the most common expression of chronic allograft dysfunction in lung transplantation. Moreover, BO represents the major cause of death in the long-term after this procedure. On the other hand, mesenchymal stem cells have been tested in animal models of BO aiming to interfere in its development. The aim of this experimental study is to explore the role of bone-marrow derived stem cells (BMSCs) as a preventive intervention of BO occurrence. Materials and methodsThis an experimental randomized study. A bronchiolitis obliterans animal model in rats was reproduced: heterotopical tracheal transplant model in lung parenchyma. Five of these animals were used as control group. After setting up the model, individuals were divided in 3 groups of treatment (n=15), in which BMSCs were administered in 3 different time points after the tracheal transplant (tracheal transplantation and BMSCs administration occurred the same day, group G0; after 7 days, group G7; after 14 days, group G14. In addition, within each group, BMSCs were administered through 3 different routes: endotracheally, endovascular and topically in the lung parenchyma). Animals were sacrificed at 21 days. Histology, fluorescence in situ hybridization and immunohistochemistry techniques were performed for identifying stem cells. ResultsCompared to control group, animals receiving BMSCs showed large neovessels in a loose fibrous matrix. Group G7 showed less fibrosis (p<0.033) and edema (p<0.028). Moreover, G7 animals receiving stem cells endotracheally showed no fibrosis (p<0.008). Alveolar-like patches of tissue were observed among all groups (53.4%, 46.7% and 40% in G0, G7 and G14 respectively), consisting of cells expressing both stem and alveolar cells biomarkers. ConclusionBMSCs modify the course of bronchiolitis obliterans and differentiate into alveolar cells. Endotracheal administration of BMSCs 7 days after the heterotopical tracheal transplant might be considered an effective way to prevent BO in this animal model.