A Novel Inflatable Surgical Device Used in Endoscopic Transplantation of Tissue Engineered Cells Sheets for Regenerative Treatments of Esophageal Ulcerations: A Preliminary Report

Abstract

Introduction: Large en-bloc resection of esophageal cancers by endoscopic submucosal dissection (ESD) often requires the use of balloon dilation after endoscopic operations to prevent post-operative esophageal constriction. We therefore have previously developed a novel method to transplant tissue engineered oral mucosal epithelial cell sheets to promote wound healing after ESD, in an effort to improve patient quality of life. (Gut, 1704-1720, 2006) Although we have demonstrated the successful transplantation of two cell sheets, it has remained difficult to transplant cell sheets to the entire surface of esophageal ulcerative wall using our previous methods using endoscopic forceps have been. We therefore sought to develop a novel device for the endoscopic delivery and transplantation of cell sheets after ESD. Methods: Oral mucosal cells harvested from a beagle were seeded on temperature-responsive dishes and cultured for 2 weeks. Oral mucosal epithelial cell sheets (24 × 24 mm2) were harvested by simply reducing the temperature. Using a novel inflatable device a carrier of the engineered tissues, four individual cell sheets were then simultaneously transplanted to an artificial circumferential esophageal ulceration of a deceased pig (n = 3). Results: A balloon is attached to the exterior of standard EEMR-tube with an outer cylindrical cover to physically protect the cell sheets and to retain moisture. For transplantation, the device is carefully moved to the ulcer site by endoscipy, the outer tube is retracted. Air is then pumped through the endoscope to distend the walls of the esophagus to allow for positioning of the cell sheets. The cell sheets are attached to the ulcer site by balloon inflation. Ten minutes after transplantation we macroscopically confirmed complete circumferential transplantation of oral mucosal cell sheets. Iodine staining indicated that the all of the cell sheets were successfully attached to the esophageal ulcer. Histological results also confirmed that the epithelial cell sheets were attached to the remnant submucosal layers. Conclusions: Our results show that this novel balloon device completely enables to the simultaneous, controlled transplantation of several tissue engineered cell sheets by endoscopy. This ability to simply cover circumferential esophageal ulcerations with a single procedure creates new a potential treatment in endoscopic treatment of Barrett's esophagus with high grade dysplasia, using ESD in conjunction with cell sheet transplantation. In the near future, we are planning in vivo experiments to the post-operative effects of cell sheet transplantation to larger ESD ulcers using the balloon device.