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

Akihiro Fujino; Yasushi Fuchimoto; Yoshiyuki Baba; Nobutaka Isogawa; Takanori Iwata; Katsuhiro Arai; Makoto Abe; Nobuo Kanai; Ryo Takagi; Masanori Maeda; Akihiro Umezawa

doi:10.1186/s13287-022-02710-9

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.

Authors

Akihiro Fujino¹, Yasushi Fuchimoto^{2

3}, Yoshiyuki Baba⁴, Nobutaka Isogawa⁴, Takanori Iwata⁵, Katsuhiro Arai⁶, Makoto Abe⁷, Nobuo Kanai⁸, Ryo Takagi^{9

10}, Masanori Maeda¹¹, Akihiro Umezawa¹⁰

Affiliations

¹ Division of Surgery, Department of Surgical Specialties, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
² Division of Surgery, Department of Surgical Specialties, National Center for Child Health and Development, Tokyo, 157-8535, Japan. yfuchimoto@iuhw.ac.jp.
³ Department of Pediatric Surgery, International University of Health and Welfare School of Medicine, Chiba, 286-8686, Japan. yfuchimoto@iuhw.ac.jp.
⁴ Division of Pedodontics and Orthodontics, Department of Surgical Specialties, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
⁵ Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
⁶ Division of Gastroenterology, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
⁷ Department of General Medicine, Kasaoka Division, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
⁸ Healthy Aging Innovation Center, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, 173-0015, Japan.
⁹ Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
¹⁰ Center for Regenerative Medicine, National Center for Child Health and Development Research Institute, Tokyo, 157-8535, Japan.
¹¹ MakeWay LLC, Saitama, 350-0461, Japan.

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 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, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393 .

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