Application of cell sheet technology for esophageal endoscopic submucosal dissection Takeshi Ohki, MD, PhD, a,b Masayuki Yamamoto, PhD, b Masaho Ota, MD, PhD, a Teruo Okano, PhD, b Masakazu Yamamoto, MD, PhD a a Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan. b Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan. Because esophageal ulceration is extensive after endoscopic submucosal dissection, we have developed a new treatment that combines endoscopic dissection with the endoscopic transplantation of oral mucosal epithelial cell sheets to prevent esophageal stenosis. Cell sheets created from the patient’s own oral mucosa were attached directly to the bed of the esophageal ulcer using endoscopic forceps immediately after endoscopic resection. The first application of regenerative medicine to endoscopic treatment was performed in 2008 and more patients are being accumulated. We are working on several advanced research methods using regenerative medicine for endoscopic treatment. © 2011 Elsevier Inc. All rights reserved. KEYWORDS: Esophageal ESD; Cell sheet Endoscopic submucosal dissection (ESD) is a standard endoscopic technique for the treatment of early gastric cancer that involves en bloc resection of a tumor of certain cancer differentiation, and lymphovascular status. 1,2 En bloc resection makes it possible to perform accurate pathologic evaluation, thus reducing the risks for lymph node metastasis and recurrent tumor to nil or lower than the morbidity and mortality of surgery. Because the risks of mortality and short- and long- term risks of mortality from endoscopic treatment are mark- edly reduced compared with surgery, extensive application of endoscopic treatment for esophageal cancer can be expected. Recently, early esophageal cancer has also been treated by ESD. 3-6 Ishihara et al 7 reported that ESD reduces the recur- rence of esophageal tumors. We have found that extensive early squamous cell carcinoma of the esophagus can be re- moved by ESD, thus avoiding surgical resection (Figure 1). However, after extensive removal by ESD, esophageal stenosis often arises because of a large ulcer at the site of tumor resection. 8 Severe esophageal stenosis occurring after endo- scopic resection is difficult to treat and can require repeated endoscopic balloon dilation (Figure 1). We are developing a new treatment for esophageal ste- nosis caused by ulceration after ESD that is based on regenerative medicine. 9 In this paper, we introduce the application of regenerative medical technology to the endo- scopic treatment of esophageal cancer. Cell sheet technology In 1993, the surgeon Prof J. Vacanti (Harvard Medical School) and the applied chemist Prof R. Langer (Massachu- setts Institute of Technology) proposed a new concept of “tissue engineering” in the journal Science. 10 Their concept was to develop new tissues using the combination of a biodegradable polymer scaffold, cells, and growth factors. This tissue engineering concept was later used in various studies on tissue regeneration. By contrast, we 11 were working on the use of temperature- responsive polymer [poly(N-isopropylacrylamide)] that was covalently bound to the surface of a temperature-responsive culture dish. This method produced an “intelligent” culture dish coated with the temperature-responsive polymer that had a hydrophobic surface at 37°C (normal culture conditions), allowing cells to attach to the surface of the dish. When the temperature was reduced to 32°C, the surface of the tempera- ture-responsive culture dish became hydrophilic and the cells were released from the dish (Figure 2). The adhesion mole- cules that maintain contact between cells are destroyed by the Address reprint requests to Takashi Ohki, MD, PhD, Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical Univer- sity, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail: ohki@ige.twmu.ac.jp Techniques in GASTROINTESTINAL ENDOSCOPY www.techgiendoscopy.com Techniques in Gastrointestinal Endoscopy (2011) 13, 105-109 1096-2883/11/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2011.01.003