Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis

Akihiro Fujino; Yasushi Fuchimoto; Teizaburo Mori; Motohiro Kano; Yohei Yamada; Michinobu Ohno; Yoshiyuki Baba; Nobutaka Isogawa; Katsuhiro Arai; Takako Yoshioka; Makoto Abe; Nobuo Kanai; Ryo Takagi; Masanori Maeda; Akihiro Umezawa

doi:10.1186/s13287-023-03321-8

Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis

Stem Cell Res Ther. 2023 Apr 13;14(1):86. doi: 10.1186/s13287-023-03321-8.

Authors

Akihiro Fujino¹, Yasushi Fuchimoto^{2

3}, Teizaburo Mori¹, Motohiro Kano¹, Yohei Yamada¹, Michinobu Ohno¹, Yoshiyuki Baba⁴, Nobutaka Isogawa⁴, Katsuhiro Arai⁵, Takako Yoshioka⁶, 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, 852, Hatakeda, Narita, 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 Division of Gastroenterology, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
⁶ Department of Pathology, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
⁷ Kasaoka Division, Department of General Medicine, 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: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in 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 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 testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations.

Results: Subject 1 had a 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. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth.

Conclusions: Subjects 2 and 3 were 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 study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis.

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; Congenital esophageal stenosis; Endoscopy; Epithelial cell sheet; Regenerative therapy; Somatic stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Constriction, Pathologic / complications
Epithelial Cells / transplantation
Esophageal Atresia* / complications
Esophageal Atresia* / surgery
Esophageal Neoplasms* / complications
Esophageal Neoplasms* / pathology
Esophageal Neoplasms* / surgery
Esophageal Stenosis* / etiology
Esophageal Stenosis* / surgery
Humans
Mouth Mucosa / transplantation
Retrospective Studies
Treatment Outcome

Associated data

UMIN-CTR/UMIN000034566