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J Thorac Cardiovasc Surg 2008;136:850-859
© 2008 The American Association for Thoracic Surgery

General Thoracic Surgery

Intrathoracic esophageal replacement by in situ tissue-engineered esophagus

Yuen Nakase, MD, PhDa,e,*, Tatsuo Nakamura, MD, PhDb, Shuichi Kin, MD, PhDa, Susumu Nakashima, MD, PhDa, Tetsuji Yoshikawa, MD, PhDa, Yoshiaki Kuriu, MD, PhDa, Chohei Sakakura, MD, PhDa, Hisakazu Yamagishi, MD, PhDa, Junji Hamuro, PhDc, Yoshito Ikada, PhDd, Eigo Otsuji, MD, PhDa, Akeo Hagiwara, MD, PhDe

a Department of Surgery and Regenerative Medicine, Division of Surgery and Physiology of Digestive System, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
b Department of Bioartificial Organs, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan
c Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
d Department of Bioenvironmental Medicine, Nara Medical University, Nara, Japan
e Department of Medical Life Systems, Doshisha University, Kyoto, Japan

Received for publication November 2, 2007; revisions received February 26, 2008; accepted for publication May 4, 2008.

* Address for reprints: Yuen Nakase, MD, PhD, Department of Surgery and Regenerative Medicine, Division of Surgery and Physiology of Digestive System, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji Kajiicho 465, Kamigyo-ku, Kyoto 602-8566, Japan. (Email: yuen-n{at}koto.kpu-m.ac.jp).

Objective: This study aimed to evaluate in situ tissue-engineered esophagus in a canine model after experimental resection and replacement of a full circumferential defect of the intrathoracic esophagus.

Methods: Two types of scaffolding were fabricated. In the KF(+) group (n = 6), oral keratinocytes and fibroblasts cultured on human amniotic membrane were sheeted on polyglycolic acid felt with smooth muscle tissue and were then rolled around tubes. In the KF(–) group (n = 6), the same procedure was followed, but the keratinocytes and fibroblasts were omitted. Both scaffolds were wrapped in omentum and implanted in the abdomen. In the KF(+) group, at 3 weeks after implantation, the scaffold developed into a tube with a well-differentiated lumen of stratified squamous cells surrounded by a thick smooth muscle-like tissue (in situ tissue-engineered esophagus). A part of the esophagus was resected and replaced by the graft in the same dogs.

Results: In the KF(–) group, strictures developed after esophageal replacement, with almost complete obstruction within 2 to 3 weeks. In contrast, in the KF(+) group, the in situ tissue-engineered esophagus showed good distensibility and the dogs remained without feeding problems through 420 days. Esophageal peristalsis transferred food to the stomach, despite the absence of peristaltic activity in the in situ tissue-engineered esophagus itself. The thickness of the squamous epithelial layer and the smooth muscle layer of the in situ tissue-engineered esophagus were similar to that of the adjacent native esophagus.

Conclusion: The in situ tissue-engineered esophagus can successfully replace the intrathoracic esophagus, and this procedure may offer a promising surgical approach to esophageal diseases.

Abbreviations and Acronyms {alpha}-SMA = {alpha}-smooth muscle actin; ITEE = in situ tissue-engineered esophagus; PBS = phosphate-buffered saline; PGA = polyglycolic acid






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