Endoscopic Transplantation of Human Oral Mucosal Epithelial Cell Sheets-World's First Case of Regenerative Medicine Applied to Endoscopic Treatment

Abstract

Background: Recently, esophageal EMR/ESD have been performed even on a huge early esophageal carcinoma in Japan. Ulcerative esophageal stricture and its treatment by painful frequent balloon dilation of the stenosis severely decrease the quality of life of patients. Previously, we reported that a novel treatment using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets successfully prevented such complications in a canine model (Gut, 55, 1704-1710, 2006). Since then, we endeavored to start the clinical research adhering to rigorous medical and ethical guidelines by Japanese FDA. After much hard work, the clinical research started in January 2008. We will present the early outcomes of the consecutive two patients. Methods: Primary epithelial cells isolated from patient's own oral mucosa were seeded on temperature responsive culture inserts without 3T3 feeder layers, and cultured with autologous serum for 2 weeks at 37°C. Oral mucosal epithelial cell sheets (23 mm in diameter) were harvested by reducing the culture temperature to 20°C. Autologous cell sheets were transplanted with endoscopic forceps onto the esophageal ulceration after EMR/ESD. Following the treatment, we observed the various stages of ulceration at intervals of one week. Results: (Case 1) A 52-year old man with a type 0-IIc esophageal carcinoma underwent esophageal EMR. A cultured autologous oral mucosal epithelial cell sheet was transplanted to the half circumferential ulceration. Three weeks after EMR, the wound healed completely. The EMR area did not contract significantly and retained its original shape and size. (Case 2) A 70-year old man with a a type 0-IIb esophageal carcinoma underwent ESD. Two cultured autologous oral mucosal epithelial cell sheets were transplanted to the 2/3 circumferential ulceration. Four weeks after ESD, complete healing was observed with no sign of constriction. Conclusions: Based on these findings, it is concluded that this treatment promotes wound healing and prevent inflammation and constriction after EMR/ESD, thereby improves post-operative quality of life of patients.