The Journal of Thoracic and Cardiovascular Surgery
Volume 136, Issue 4 , Pages 850-859, October 2008

Intrathoracic esophageal replacement by in situ tissue-engineered esophagus

  • Yuen Nakase, MD, PhD

      Affiliations

    • 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
    • Department of Medical Life Systems, Doshisha University, Kyoto, Japan
    • Corresponding Author InformationAddress 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.
  • ,
  • Tatsuo Nakamura, MD, PhD

      Affiliations

    • Department of Bioartificial Organs, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan
  • ,
  • Shuichi Kin, MD, PhD

      Affiliations

    • 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
  • ,
  • Susumu Nakashima, MD, PhD

      Affiliations

    • 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
  • ,
  • Tetsuji Yoshikawa, MD, PhD

      Affiliations

    • 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
  • ,
  • Yoshiaki Kuriu, MD, PhD

      Affiliations

    • 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
  • ,
  • Chohei Sakakura, MD, PhD

      Affiliations

    • 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
  • ,
  • Hisakazu Yamagishi, MD, PhD

      Affiliations

    • 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
  • ,
  • Junji Hamuro, PhD

      Affiliations

    • Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • ,
  • Yoshito Ikada, PhD

      Affiliations

    • Department of Bioenvironmental Medicine, Nara Medical University, Nara, Japan
  • ,
  • Eigo Otsuji, MD, PhD

      Affiliations

    • 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
  • ,
  • Akeo Hagiwara, MD, PhD

      Affiliations

    • Department of Medical Life Systems, Doshisha University, Kyoto, Japan

Received 2 November 2007; received in revised form 26 February 2008; accepted 4 May 2008. published online 11 August 2008.

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: α-SMA, α-smooth muscle actin, ITEE, in situ tissue-engineered esophagus, PBS, phosphate-buffered saline, PGA, polyglycolic acid

CTSNet classification: 8

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 This work was supported in part by a grant for the Third-Term Comprehensive 10-Year Strategy of Cancer Control from the Ministry of Health, Labor and Welfare of Japan.

PII: S0022-5223(08)01046-5

doi:10.1016/j.jtcvs.2008.05.027

The Journal of Thoracic and Cardiovascular Surgery
Volume 136, Issue 4 , Pages 850-859, October 2008