Pilot study of autologous multilayered fibroblast sheet transplantation for reinforcing bronchial stump healing after pulmonary lobectomy in a canine model.

Abstract

OBJECTIVE: Bronchopleural fistula (BPF) is a serious complication that can occur after lung resection. This pilot study aimed to evaluate the effectiveness of autologous multilayered fibroblast sheet transplantation in reinforcing bronchial stump healing after lung resection in a canine model. METHODS: Four beagles underwent left caudal lobe excision. Two dogs received autologous multilayered fibroblast sheet transplantation on the stapled bronchial stump, while two served as controls. Fibroblast sheets generated from autologous oral mucosal fibroblasts were optimized for growth factor secretion. Fourteen days after lobectomy, the bronchial stumps were histologically and immunohistochemically analyzed to assess connective tissue formation, blood vessel formation, and inflammation. RESULTS: Fibroblast sheets secreted high levels of pro-healing and pro-angiogenic factors in vitro. No adverse events or serious postoperative complications associated with the fibroblast sheet transplantation were observed. The cell sheet-transplanted group exhibited a layered structure of newly formed tissue around the bronchial stump. This was associated with enhanced blood vessel formation, as indicated by increased CD31-positive cells and high VEGF levels. The untreated control group showed a localized nodule of inflammation near the bronchial stump, which lacked evidence of blood vessel formation. CONCLUSION: Autologous multilayered fibroblast sheet transplantation promoted connective tissue formation and blood vessel growth around the bronchial stump after lobectomy in a canine model. These findings suggest that fibroblast sheet transplantation is a promising therapeutic approach for preventing BPF after lung resection.