Takeshi Ohki1, Masayuki Yamato2, Masaho Ota3, Ryo Takagi2, Daisuke Murakami4, Makoto Kondo4, Ryo Sasaki5, Hideo Namiki6, Teruo Okano7, Masakazu Yamamoto3. 1. Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan; Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan. 2. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan. 3. Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan. 4. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan; Graduate School of Science and Engineering, Waseda University, Tokyo, Japan. 5. Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, Tokyo, Japan. 6. Graduate School of Science and Engineering, Waseda University, Tokyo, Japan. 7. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan. Electronic address: tokano@abmes.twmu.ac.jp.
Abstract
BACKGROUND & AIMS: The use of esophageal endoscopic submucosal dissection (ESD) to remove superficial esophageal neoplasms is gradually becoming more common in Japan. However, large-scale esophageal ESD often requires subsequent multiple balloon dilations to prevent postoperative esophageal stricture. We investigated the safety and efficacy of endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in preventing formation of strictures after ESD. METHODS: We performed an open-label, single-arm, single-institute study. We collected specimens of oral mucosal tissue from 9 patients with superficial esophageal neoplasms. Epithelial cell sheets were fabricated ex vivo by culturing isolated cells for 16 days on temperature-responsive cell culture surfaces. After a reduction in temperature, these sheets were endoscopically transplanted directly to the ulcer surfaces of patients who had just undergone ESD. All patients were monitored by endoscopy once a week until epithelialization was complete. RESULTS: Autologous cell sheets were successfully transplanted to ulcer surfaces using an endoscope. Complete re-epithelialization occurred within a median time of 3.5 weeks. No patients experienced dysphagia, stricture, or other complications following the procedure, except for one patient who had a full circumferential ulceration that expanded to the esophagogastric junction. CONCLUSIONS: Sutureless, endoscopic transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells safely and effectively promotes re-epithelialization of the esophagus after ESD. Patients in this study did not experience any serious complications. This procedure might be used to prevent stricture formation following ESD and improve patients' quality of life. Further study will be needed to show that stricture formation can be prevented.
BACKGROUND & AIMS: The use of esophageal endoscopic submucosal dissection (ESD) to remove superficial esophageal neoplasms is gradually becoming more common in Japan. However, large-scale esophageal ESD often requires subsequent multiple balloon dilations to prevent postoperative esophageal stricture. We investigated the safety and efficacy of endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in preventing formation of strictures after ESD. METHODS: We performed an open-label, single-arm, single-institute study. We collected specimens of oral mucosal tissue from 9 patients with superficial esophageal neoplasms. Epithelial cell sheets were fabricated ex vivo by culturing isolated cells for 16 days on temperature-responsive cell culture surfaces. After a reduction in temperature, these sheets were endoscopically transplanted directly to the ulcer surfaces of patients who had just undergone ESD. All patients were monitored by endoscopy once a week until epithelialization was complete. RESULTS: Autologous cell sheets were successfully transplanted to ulcer surfaces using an endoscope. Complete re-epithelialization occurred within a median time of 3.5 weeks. No patients experienced dysphagia, stricture, or other complications following the procedure, except for one patient who had a full circumferential ulceration that expanded to the esophagogastric junction. CONCLUSIONS: Sutureless, endoscopic transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells safely and effectively promotes re-epithelialization of the esophagus after ESD. Patients in this study did not experience any serious complications. This procedure might be used to prevent stricture formation following ESD and improve patients' quality of life. Further study will be needed to show that stricture formation can be prevented.
Authors: Eduard Jonas; Sebastian Sjöqvist; Peter Elbe; Nobuo Kanai; Jenny Enger; Stephan L Haas; Ammar Mohkles-Barakat; Teruo Okano; Ryo Takagi; Takeshi Ohki; Masakazu Yamamoto; Makoto Kondo; Katrin Markland; Mei Ling Lim; Masayuki Yamato; Magnus Nilsson; Johan Permert; Pontus Blomberg; J-Matthias Löhr Journal: United European Gastroenterol J Date: 2016-02-19 Impact factor: 4.623