Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model

PLoS One. 2016 Mar 1;11(3):e0148249. doi: 10.1371/journal.pone.0148249. eCollection 2016.

Abstract

Background & aims: Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation.

Methods: Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed.

Results: One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6 (17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052).

Conclusion: In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture's rate.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / pathology
  • Animals
  • Cell Culture Techniques
  • Cells, Cultured
  • Dissection
  • Endoscopy, Gastrointestinal / adverse effects*
  • Esophageal Neoplasms / surgery
  • Esophageal Stenosis / etiology
  • Esophageal Stenosis / prevention & control*
  • Esophagus / diagnostic imaging
  • Esophagus / pathology
  • Female
  • Postoperative Complications / prevention & control*
  • Radiography
  • Stem Cell Transplantation / methods*
  • Sus scrofa

Grants and funding

Université Paris Descartes Sorbonne Paris cité, UMR-S970, 56 rue Leblanc, 75015 Paris, France and the Fondation de l’avenir pour la recherche médicale appliquée, 255 rue de Vaugirard, 75719 Paris cedex 15, Paris, France supported the study. http://www.fondationdelavenir.org/fondation/fondation-de-l-avenir-pour-la-recherche-medicale-appliquee.htm. GP and GR received the fundings. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.