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Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model
  1. T Ohki1,
  2. M Yamato2,
  3. D Murakami3,
  4. R Takagi2,
  5. J Yang2,
  6. H Namiki3,
  7. T Okano2,
  8. K Takasaki1
  1. 1Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
  2. 2Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan
  3. 3Graduate School of Science and Engineering, Waseda University, Tokyo, Japan
  1. Correspondence to:
    T Okano
    Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; tokano{at}abmes.twmu.ac.jp

Abstract

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.

Aims: 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°C, on temperature-responsive dishes. After ESD (5 cm in length, 180° in range), cell sheets were harvested by a simple reduction in temperature to 20°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.

  • ECM, extracellular matrix
  • EMR, endoscopic mucosal resection
  • ESD, endoscopic submucosal dissection
  • H&E, haematoxylin and eosin
  • PVDF, polyvinylidene difluoride

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Footnotes

  • Published Online First 18 May 2006

  • Funding: This work was supported in part by the Center of Excellence (COE) Program for the 21st Century, the High-Tech Research Center Program, and the Support Program for Contemporary Educational Needs (Gendai GP) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; the Core Research for Evolution Science and Technology Program (CREST) by the Japan Science and Technology Agency (JST); and the Core To Core Program from the Japan Society for the Promotion of Science (JSPS).

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