title: Circumferential esophageal replacement using a tube-shaped tissue-engineered substitute: An experimental study in minipigs.
abstract: BACKGROUND
  Esophageal replacement by the colon or the stomach for malignant and nonmalignant esophageal diseases exposes to significant morbidity and mortality. In this setting, tissue engineering seems to be a seductive alternative.
  
  
  METHODS
  In a porcine model, we performed a 5-cm-long circumferential replacement of the cervical esophagus by a tubulized acellular matrix (small intestinal submucosa) cellularized with autologous skeletal myoblasts and covered by a human amniotic membrane seeded with autologous oral epithelial cells. The substitute was grown for 2 weeks in the great omentum before esophageal replacement. Eighteen minipigs (divided into 3 groups: group A [substitute with esophageal endoprothesis; n = 6], group B [substitute alone; n = 6], and group C [endoprothesis alone; n = 6]) were included. The esophageal endoprothesis was removed at 6 months. Animals were killed sequentially over a 12 month-period. Clinical, endoscopic, radiologic and histologic outcomes were analyzed.
  
  
  RESULTS
  All animals except 1 of in groups B and C died during the first 2 months owing to refractory esophageal stenosis or endoprothesis extrusion. Nutritional autonomy without endoprothesis was observed in all animals of group A with a follow-up of >6 months (n = 3). A phenotype similar to that of native esophagus, consisting of a mature epithelium, submucosal glands, and a circular muscular layer, was observed after 9 months.
  
  
  CONCLUSIONS
  In this model, the circumferential replacement of the cervical esophagus by a tube-shaped tissue-engineered substitute under the temporary cover of an esophageal endoprothesis allowed nutritional autonomy and tissue remodeling toward an esophageal phenotype.
authors: Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France; Department of Digestive and Endocrine Surgery, Saint-Louis Hospital, AP-HP, Paris, France; Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: tpoghosyan@yahoo.com.
authors: Tigran
authors: T
authors: Poghosyan
authors: Department of Pediatric Surgery, Jeanne de Flandre Hospital and Université Lille 2, Lille, France.
authors: Rony
authors: R
authors: Sfeir
authors: Reference Center for Congenital and Malformative Esophageal Diseases, Department of Pediatric Gastroenterology and Nutrition, Jeanne de Flandre Hospital and Université Lille 2, Lille, France.
authors: Laurent
authors: L
authors: Michaud
authors: Department of Pathology, Georges Pompidou European Hospital, AP-HP, Paris, France.
authors: Patrick
authors: P
authors: Bruneval
authors: Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France.
authors: Thomas
authors: T
authors: Domet
authors: Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France; Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors: Valerie
authors: V
authors: Vanneaux
authors: Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France; Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors: Minh
authors: M
authors: Luong-Nguyen
authors: Department of Digestive and Endocrine Surgery, Cochin Hospital, AP-HP, Paris, France.
authors: Sebastien
authors: S
authors: Gaujoux
authors: Reference Center for Congenital and Malformative Esophageal Diseases, Department of Pediatric Gastroenterology and Nutrition, Jeanne de Flandre Hospital and Université Lille 2, Lille, France.
authors: Frederic
authors: F
authors: Gottrand
authors: Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France; Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors: Jerome
authors: J
authors: Larghero
authors: Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France; Department of Digestive and Endocrine Surgery, Saint-Louis Hospital, AP-HP, Paris, France; Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors: Pierre
authors: P
authors: Cattan
mesh_terms: D000818:Animals; D001187:Artificial Organs; D004947:Esophagus / Q000601:surgery*; D007421:Intestine, Small / Q000637:transplantation; D008297:Male; D023421:Models, Animal; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering; D054457:Tissue Scaffolds