Successful use of bio plugs for delayed bronchial closure after pneumonectomy in experimental settings

OBJECTIVES: Cell therapies, such as stem cell suspension injection, are used to treat bronchopleural fistula. Although it is safe and effective, injected cells cannot remain within the bronchioles of the fistula due to cell leakage into the thoracic cavity. Here, we inserted a 'bio plug' into the fistula, produced using cells and a bio-3D printer, to examine the effectiveness of bio plugs for the closure of bronchopleural fistulas, the optimal cell source and the closure mechanism. METHODS: Bio plugs were made with mesenchymal stem (stromal) cells derived from bone marrow (MSCBM), fibroblasts and rat lung micro-vessel endothelial cells using a bio-3D printer with different cell mixing ratios. Six groups, according to the presence or absence and the type of bio plugs, were compared. The plugs were inserted into the bronchi of F344 rats. The obstruction ratio and histological and immunohistochemical findings were evaluated. RESULTS: MSCBM+ rat lung micro-vessel endothelial cell group exhibited a higher obstruction ratio among all groups excluding the MSCBM group (P = 0.039). This group had fibrosis and CD31-positive cells and fewer CD68-positive cells than MSCBM and MSCBM+ fibroblast groups. CONCLUSIONS: Bio plugs with mixed cells, including stem cells, contribute to bronchial closure in the current experimental setting. Endothelial cells effectively maintain the structure in this model. Although bronchial closure for bronchopleural fistula could not be described as clinical conditions were not reproduced, we collected essential data on bronchial closure; however, further experiments are warranted.