Background: We performed the world's first autologous oral mucosa-derived epithelial cell sheet transplantation therapy for a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis (CES) were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy. Methods: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control tests, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations. Results: Subject 1 had the stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subject 2 did not require EBD for more than 18 months after transplantation, and Subject 3 did not require EBD for at least 9 months after transplantation, during which time they were able to take normal diet by mouth. Conclusions: Subject 2 was free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to accumulate cases and deepen the research to solve further problems, such as the study of an objective index to evaluate the efficacy of cell sheet transplantation therapy, the development of a new device to achieve more accurate transplantation, the study of cases in which the current therapy is effective and the optimal timing of transplantation, and the clarification of the mechanism by which the current therapy improves stenosis.

AU is a co-researcher with CellSeed Inc. MM is the CEO of MakeWay LLC. The other authors have no conflicts of interest regarding the work described herein.

UMIN000034566

This research was supported by AMED (JP18bk0104006, JP22bk0104140).

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The entire study including the clinical intervention component and experiments with human cells and tissues was approved by the Institutional Review Board and Certified Special Committee for Regenerative Medicine at the National Center for Child Health and Development. Human cells in this study were utilized in full compliance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects (Ministry of Health, Labor, and Welfare (MHLW), Japan; Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan). Informed consent to participate in this study was obtained from the parents of the patients.

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