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

Takeshi Ohki ¹, Masayuki Yamato ¹, Daisuke Murakami ², Ryo Takagi ¹, Joseph Yang ¹, Hideo Namiki ², Teruo Okano ^1* and Ken Takasaki ¹

¹ Tokyo Women's Medical University, Japan
² Waseda University, Japan

^* To whom correspondence should be addressed. E-mail: tokano{at}abmes.twmu.ac.jp.

Accepted 6 May 2006

Abstract

Background: With the recent development of endoscopic submucosal dissection (ESD), large oesophageal cancers can be removed with a single procedure with little limits on the resectable range. However, after aggressive ESD, a major complication that arises is the post-operative inflammation and stenosis that can significantly affect the patient's quality of life.

Aims: We examined 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 simple temperature reduction to 20°C, and transplanted by endoscopy.

Results: The transplanted cell sheets were able to adhere and survive on the underlying muscle layers within 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. In 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 demonstrate the effectiveness of a novel combined endoscopic approach for the potential treatment of oesophageal cancers that can effectively enhance wound healing and possibly prevent post-operative oesophageal stenosis.

Keywords: autologous cell sheet, endoscopic submucosal dissection, endoscopic transplantation, oesophagus

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