Tracheal reconstruction by mesenchymal stem cells with small intestine submucosa in rabbits

Aim: The increasing number of newborns requiring intubation and artificial ventilation in the sophisticated premature and intensive care units of recent years has been followed by a concomitant increase in the number of children who develop tracheal stenosis as a sequela of prolonged intubation, with a consequent increasing need for tracheal surgical repair. The aim of this study was to evaluate tracheal reconstruction by monolayered autologous mesenchymal stem cells (MSCs) with small intestine submucosa (SIS) in a rabbit model. Methods: Twelve male rabbits were randomly divided into three groups: rabbits with tracheal defects without reconstruction (untreated group, n= 4), rabbits with tracheal defects given porcine small intestine submucosa graft (SIS group, n= 4), and rabbits with tracheal defects that underwent transplantation of monolayered mesenchymal stem cells on SIS (SIS+MSC group, n= 4). Histological and endoscopic analyses were performed by hematoxylin-eosin staining (H&E), Prussian blue staining and endoscopy. Results: Tracheal stenosis in the SIS+MSC group was minimal, compared to the untreated group and SIS group. Specimens obtained from the untreated and SIS groups showed severe infiltration of inflammatory cells and granulation tissue formation into the trachea. In the SIS+MSC group, however, minimal infiltration of the inflammatory cells and granulation tissue formation were observed. Twelve weeks following the operation, regeneration of pseudostratified columnar epithelium was confirmed by H&E staining with minimal inflammatory cell infiltration in the SIS+MSC group. Moreover, Prussian blue staining clearly demonstrated the presence of labeled MSCs in the regenerated tissue of SIS+MSC group. Conclusions: These results demonstrate that tracheal reconstruction by MSCs with SIS is effective in rabbits with tracheal defects with minimal mortality and morbidity, which appears to be a promising strategy in the treatment of tracheal defects.