Circumferential esophageal replacement using a tube-shaped tissue-engineered substitute: An experimental study in minipigs

Abstract

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. 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 2weeks 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 6months. Animals were killed sequentially over a 12 month-period. Clinical, endoscopic, radiologic and histologic outcomes were analyzed. All animals except 1 of in groups B and C died during the first 2months 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 >6months (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 9months. 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.