First-in-human autologous oral mucosal epithelial sheet transplantation to prevent anastomotic re-stenosis in congenital esophageal atresia

Abstract

Background: Congenital esophageal atresia postoperative anastomotic stricture occurs in 30-50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. Methods: Epithelial cell sheets were fabricated from a patient s oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. Results: The number of EBDs required after transplantation and the number of days between EDBs were recorded. Before transplantation, EBDs were performed approximately every two weeks, whereas after transplantation, the interval was extended to a maximum of four weeks. The patient was also aware of a reduction in dysphagia. Conclusions: This study suggests that cell sheet transplantation might be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia. We chose this very severe case for the first clinical study in humans. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation.