Keisuke Suzuki1, Makoto Komura2, Kazuko Obana3, Hiroko Komura4, Ryoko Inaki5, Jun Fujishiro6, Kan Suzuki6, Yasuhide Nakayama7. 1. Department of Pediatric Surgery, Saitama Medical University, Saitama, Japan; Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 2. Department of Pediatric Surgery, Saitama Medical University, Saitama, Japan; Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Division of Tissue engineering, The University of Tokyo Hospital, Tokyo, Japan. Electronic address: komura-tky@umin.ac.jp. 3. Department of Pediatric Surgery, Saitama Medical University, Saitama, Japan. 4. Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Division of Tissue engineering, The University of Tokyo Hospital, Tokyo, Japan. 5. Division of Tissue engineering, The University of Tokyo Hospital, Tokyo, Japan. 6. Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 7. Biotube Co., Ltd, Osaka, Japan.
Abstract
PURPOSE: Tissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect. METHOD: The cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis. RESULTS: Postoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin. CONCLUSION: Orthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.
PURPOSE: Tissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect. METHOD: The cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis. RESULTS: Postoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin. CONCLUSION: Orthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.