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.

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.