Tigran Poghosyan1, Rony Sfeir2, Laurent Michaud3, Patrick Bruneval4, Thomas Domet5, Valerie Vanneaux6, Minh Luong-Nguyen6, Sebastien Gaujoux7, Frederic Gottrand3, Jerome Larghero6, Pierre Cattan8. 1. 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. 2. Department of Pediatric Surgery, Jeanne de Flandre Hospital and Université Lille 2, Lille, France. 3. Reference Center for Congenital and Malformative Esophageal Diseases, Department of Pediatric Gastroenterology and Nutrition, Jeanne de Flandre Hospital and Université Lille 2, Lille, France. 4. Department of Pathology, Georges Pompidou European Hospital, AP-HP, Paris, France. 5. Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France. 6. Cell Therapy Unit and CIC-BT, Saint-Louis Hospital, AP-HP, Paris, France; Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 7. Department of Digestive and Endocrine Surgery, Cochin Hospital, AP-HP, Paris, France. 8. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Tiffany L Sarrafian; Jennifer L Brazzell; Matthew Barron; Johnathon Aho; Ellen Blanco; Chelsea Powell; Jed Johnson; Dennis A Wigle Journal: J Thorac Dis Date: 2022-06 Impact factor: 3.005