Successful prevention of esophageal stricture after ESD using 2 tissue-engineered cellular film sheets Treatment of superficial neoplastic esophageal lesions with esophageal ESD is becoming increasingly common. However, multiple balloon dilatations are required to prevent esophageal stricture after large esophageal ESD. To evaluate the safety and efficacy of endoscopic transplantation of tissue-engineered cell membranes to prevent esophageal strictures after ESD, Takeshi OHKI, an expert from the Japanese Institute of Gastroenterology, conducted this study. The results of the study were published in GASTROENTEROLOGY Vol. 143, No. 3 in 2012. The study included nine patients with superficial esophageal neoplastic lesions who were prepared for esophageal ESD surgery, and after disinfection of the oral cavity with iodophor, under local anesthesia with lidocaine, separate oral mucosal tissue specimens of approximately 6 mm in size were collected from the buccal portion of the lateral side of the oral cavity. (1000 PU/mL) for 2 h at 37°C to obtain oral mucosal epithelial cells, followed by the addition of trypsin and ethylenediaminetetraacetic acid for 20 min, and finally individual oral mucosal epithelial cells. The isolated individual epithelial cells were cultured at 37°C for 16 days in a previously prepared temperature-sensitive cell culture. This temperature-sensitive cell culture is able to change its hydration properties with temperature changes, facilitating cell adhesion and growth at 37°C. After cooling to 20°C, the surface rapidly hydrates and swells, facilitating the dissociation of cell membrane sheets from the culture. The process does not require protein hydrolase and ethylenediaminetetraacetic acid treatment. Cell membrane sheets of approximately 23.4 mm in size were harvested. The obtained cell membrane pieces were then endoscopically transplanted directly onto the ulcer surface of the post-ESD patient. All patients underwent weekly endoscopy until the ulcer surface epithelium was fully formed. During this study, the autologous-derived cell sheets were successfully transplanted endoscopically onto the ulcer surface. After a mean of 3.5 weeks, epithelial cells on the ulcer surface were fully formed. With the exception of one total circumferential resection patient who formed a circumferential ulcer extending into the gastroesophageal junction (see below for details), all eight patients experienced no dysphagia, stricture, or other complications. The total circumferential resected patient developed an 11 cm diameter esophageal ulcer that extended to the gastroesophageal junction. Seven tissue-engineered cellular membrane pieces were transplanted in the posterior wall of the esophagus, as demonstrated endoscopically one week later. Endoscopically, the epithelial tissue in the posterior wall was thicker than the epithelial tissue in the anterior wall. The patient underwent 21 endoscopic balloon dilations. This patient had a MellowCPinkas score of 2 (only semi-solid food could be swallowed) for dysphagia symptoms. After esophageal ESD, the esophageal mucosa contracted and the markers on the mucosa moved centripetally, causing esophageal mucosal wrinkling. This study showed that the transplanted cellular membrane sheet was able to maintain the original shape and size of the resected area, resulting in minimal esophageal mucosal shrinkage. The results of this study suggest that cells derived from autologous oral mucosal epithelium, manufactured ex vivo into tissue-engineered epithelial cell membrane sheets, can serve to reconstruct the surface of the esophageal lumen and prevent esophageal stricture in patients after esophageal ESD. This improves the quality of life of the patient. The authors suggest that the transplanted cells may serve as a cell source for regenerating epithelial cells, or the transplanted cell membrane sheets may secrete growth factors and cytokines to promote ulcer healing. The authors concluded that the study still needs long-term follow-up and more cases to evaluate the long-term effectiveness and safety of the technique, offering the possibility of ESD for the treatment of large esophageal mucosal cancers. Although the case involved in this study was only a Japanese squamous cell carcinoma, the technique may be equally effective in Barrett’s esophagus due to similar complications after ESD in Barrett’s esophagus.