Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model.
BACKGROUND
With the recent development of endoscopic submucosal dissection (ESD), large oesophageal cancers can be removed with a single procedure, with few limits on the resectable range. However, after aggressive ESD, a major complication that arises is postoperative inflammation and stenosis that can considerably affect the patient's quality of life.


OBJECTIVE
To examine 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 degrees C, on temperature-responsive dishes. After ESD (5 cm in length, 180 degrees in range), cell sheets were harvested by a simple reduction in temperature to 20 degrees C, and transplanted by endoscopy.


RESULTS
The transplanted cell sheets were able to adhere to and survive on the underlying muscle layers in 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. By 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 show the effectiveness of a novel combined endoscopic approach for the potential treatment of oesophageal cancers that can effectively enhance wound healing and possibly prevent postoperative oesophageal stenosis.
Ohki
T
T
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Yamato
M
M
Murakami
D
D
Takagi
R
R
Yang
J
J
Namiki
H
H
Okano
T
T
Takasaki
K
K
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004847:Epithelial Cells / Q000637:transplantation*; D004935:Esophageal Diseases / Q000473:pathology / Q000601:surgery*; D004938:Esophageal Neoplasms / Q000601:surgery; D004940:Esophageal Stenosis / Q000473:pathology / Q000517:prevention & control; D004945:Esophagoscopy / Q000379:methods; D004947:Esophagus / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009061:Mouth Mucosa / Q000166:cytology*; D011183:Postoperative Complications / Q000601:surgery; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome; D014456:Ulcer / Q000473:pathology / Q000601:surgery*; D014945:Wound Healing / Q000502:physiology