title: ADSC-sheet Transplantation to Prevent Stricture after Extended Esophageal Endoscopic Submucosal Dissection.
abstract: In past years, the cell-sheet construct has spurred wide interest in regenerative medicine, especially for reconstructive surgery procedures. The development of diversified technologies combining adipose tissue-derived stromal cells (ADSCs) with various biomaterials has led to the construction of numerous types of tissue-engineered substitutes, such as bone, cartilage, and adipose tissues from rodent, porcine, or human ADSCs. Extended esophageal endoscopic submucosal dissection (ESD) is responsible for esophageal stricture formation. Stricture prevention remains challenging, with no efficient treatments available. Previous studies reported the effectiveness of mucosal cell-sheet transplantation in a canine model and in humans. ADSCs are attributed anti-inflammatory properties, local immune modulating effects, neovascularization induction, and differentiation abilities into mesenchymal and non-mesenchymal lineages. This original study describes the endoscopic transplantation of an ADSC tissue-engineered construct to prevent esophageal stricture in a swine model. The ADSC construct was composed of two allogenic ADSC sheets layered upon each other on a paper support membrane. The ADSCs were labeled with the PKH67 fluorophore to allow probe-based confocal laser endomicroscopy (pCLE) monitoring. On the day of transplantation, a 5-cm and hemi-circumferential ESD known to induce esophageal stricture was performed. Animals were immediately endoscopically transplanted with 4 ADSC constructs. The complete adhesion of the ADSC constructs was obtained after 10 min of gentle application. Animals were sacrificed on day 28. All animals were successfully transplanted. Transplantation was confirmed on day 3 with a positive pCLE evaluation. Compared to transplanted animals, control animals developed severe strictures, with major fibrotic tissue development, more frequent alimentary trouble, and reduced weight gain. In our model, the transplantation of allogenic ADSCs, organized in double cell sheets, after extended ESD was successful and strongly associated with a lower esophageal stricture rate.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; Department of Gastroenterology, Hôpital Européen Georges Pompidou; UMR-S970, Université Paris Descartes Sorbonne Paris Cité.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Perrod
authors.affiliation: UMR-S970, Université Paris Descartes Sorbonne Paris Cité.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Pidial
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; Department of Pathology, Hôpital Européen Georges Pompidou.
authors.forename: Sophie
authors.initials: S
authors.lastname: Camilleri
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; UMR-S970, Université Paris Descartes Sorbonne Paris Cité; Department of Radiology, Hôpital Européen Georges Pompidou.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bellucci
authors.affiliation: UMR-S970, Université Paris Descartes Sorbonne Paris Cité.
authors.forename: Amaury
authors.initials: A
authors.lastname: Casanova
authors.affiliation: UMR-S970, Université Paris Descartes Sorbonne Paris Cité.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; UMR-S970, Université Paris Descartes Sorbonne Paris Cité; Department of Radiology, Hôpital Européen Georges Pompidou.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; Department of Gastroenterology, Hôpital Européen Georges Pompidou.
authors.forename: Chirstophe
authors.initials: C
authors.lastname: Cellier
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; UMR-S970, Université Paris Descartes Sorbonne Paris Cité; Department of Radiology, Hôpital Européen Georges Pompidou.
authors.forename: Olivier
authors.initials: O
authors.lastname: Clément
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité; Department of Gastroenterology, Hôpital Européen Georges Pompidou; UMR-S970, Université Paris Descartes Sorbonne Paris Cité; gabriel.rahmi@aphp.fr.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rahmi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004210:Dissection / Q000379:methods; D000069916:Endoscopic Mucosal Resection; D004940:Esophageal Stenosis / Q000517:prevention & control*; D005260:Female; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control*; D044968:Regenerative Medicine; D017154:Stromal Cells / Q000637:transplantation*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D019737:Transplants