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

Stem Cell Res Ther. 2022 Jan 28;13(1):35. doi: 10.1186/s13287-022-02710-9.


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 dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation.

Conclusions: These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation.

Trial registration: UMIN, UMIN000034566, registered 19 October 2018, .

Keywords: Anastomotic stenosis; Cell sheet transplantation; Congenital esophageal atresia; Epithelial cell sheet; Regenerative therapy; Somatic stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Constriction, Pathologic / complications
  • Constriction, Pathologic / therapy
  • Esophageal Atresia* / complications
  • Esophageal Atresia* / surgery
  • Esophageal Stenosis* / prevention & control
  • Esophageal Stenosis* / surgery
  • Humans
  • Mouth Mucosa / transplantation
  • Retrospective Studies
  • Treatment Outcome

Associated data

  • JPRN/UMIN000034566