Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model

• Published in: Gut Vol. 55; no. 12; pp. 1704 - 1710
• Main Authors: Ohki, T, Yamato, M, Murakami, D, Takagi, R, Yang, J, Namiki, H, Okano, T, Takasaki, K
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.12.2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Animals; Biological and medical sciences; Cancer; Disease Models, Animal; Dissection; Dogs; ECM; EMR; endoscopic mucosal resection; endoscopic submucosal dissection; Endoscopy; Epithelial Cells - transplantation; ESD; Esophageal Diseases - pathology; Esophageal Diseases - surgery; Esophageal Neoplasms - surgery; Esophageal Stenosis - pathology; Esophageal Stenosis - prevention & control; Esophagoscopy - methods; Esophagus; Esophagus - pathology; Esophagus - surgery; extracellular matrix; Gastroenterology. Liver. Pancreas. Abdomen; H&E; haematoxylin and eosin; Immunohistochemistry - methods; Inflammation; Male; Medical sciences; Microscopy, Electron, Scanning - methods; Mouth Mucosa - cytology; Oesophagus; Other diseases. Semiology; polyvinylidene difluoride; Postoperative Complications - surgery; PVDF; Tissue Engineering - methods; Treatment Outcome; Ulcer - pathology; Ulcer - surgery; Ulcers; Wound healing; Wound Healing - physiology; United States > US; Japan; Cell culture; Animal model; Hemostatic; Mucosa; Esophageal disease; Esophageal stenosis; Transplantation; Autograft; Graft; Complication; Submucosa; Endoscopy; Ulceration; Dog; Human; Postoperative; Fissipedia; Carnivora; Oral administration; Inflammation; Malignant tumor; Esophagus; Quality of life; Vertebrata; Mammalia; Treatment; Animal; Digestive diseases; Epithelial cell; Models; Cancer
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gut.2005.088518

Background: With the recent development of endoscopic submucosal dissection (ESD), large oesophageal cancers can be removed with a single procedure, with few limits on the resectable range. However, after aggressive ESD, a major complication that arises is postoperative inflammation and stenosis that can considerably affect the patient’s quality of life. Aims: To examine a novel treatment combining ESD and the endoscopic transplantation of tissue-engineered cell sheets created using autologous oral mucosal epithelial cells, in a clinically relevant large animal model. Methods: Oral mucosal epithelial cells, harvested from beagle dogs, were cultured under normal conditions at 37°C, on temperature-responsive dishes. After ESD (5 cm in length, 180° in range), cell sheets were harvested by a simple reduction in temperature to 20°C, and transplanted by endoscopy. Results: The transplanted cell sheets were able to adhere to and survive on the underlying muscle layers in the ulcer sites, providing an intact, stratified epithelium. Four weeks after surgery, complete wound healing, with no observable stenosis, was seen in the animals receiving autologous cell sheet transplantation. By contrast, noticeable fibrin mesh and host inflammation, consistent with the intermediate stages of wound healing, were observed in the control animals that received only ESD. Conclusions: These findings in a clinically relevant canine model show the effectiveness of a novel combined endoscopic approach for the potential treatment of oesophageal cancers that can effectively enhance wound healing and possibly prevent postoperative oesophageal stenosis.