Human-Scale Whole-Organ Bioengineering for Liver Transplantation: A Regenerative Medicine Approach

  • Hiroshi Yagi
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Ken Fukumitsu
    Department of Pathology, Center for Innovative Regenerative Therapies, Department of Surgery, Transplantation Section, Children's Hospital of Pittsburgh and the Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
  • Kazumasa Fukuda
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Minoru Kitago
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Masahiro Shinoda
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Hideaki Obara
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Osamu Itano
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Shigeyuki Kawachi
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Minoru Tanabe
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  • Gina M. Coudriet
    Department of Pediatrics, Division of Immunogenetics /Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
  • Jon D. Piganelli
    Department of Pediatrics, Division of Immunogenetics /Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
  • Thomas W. Gilbert
    McGowan Institute for Regenerative Medicine, Departments of Surgery, Cardiothoracic Surgery, and Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
  • Alejandro Soto-Gutierrez
    Department of Pathology, Center for Innovative Regenerative Therapies, Department of Surgery, Transplantation Section, Children's Hospital of Pittsburgh and the Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
  • Yuko Kitagawa
    Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan

書誌事項

公開日
2013-02
資源種別
journal article
権利情報
  • http://journals.sagepub.com/page/policies/text-and-data-mining-license
DOI
  • 10.3727/096368912x654939
公開者
SAGE Publications

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<jats:p>At this time, the only definitive treatment of hepatic failure is liver transplantation. However, transplantation has been limited by the severely limited supply of human donor livers. Alternatively, a regenerative medicine approach has been recently proposed in rodents that describe the production of three-dimensional whole-organ scaffolds for assembly of engineered complete organs. In the present study, we describe the decellularization of porcine livers to generate liver constructs at a scale that can be clinically relevant. Adult ischemic porcine livers were successfully decellularized using a customized perfusion protocol, the decellularization process preserved the ultrastructural extracellular matrix components, functional characteristics of the native microvascular and the bile drainage network of the liver, and growth factors necessary for angiogenesis and liver regeneration. Furthermore, isolated hepatocytes engrafted and reorganized in the porcine decellularized livers using a human-sized organ culture system. These results provide proof-of-principle for the generation of a human-sized, three-dimensional organ scaffold as a potential structure for human liver grafts reconstruction for transplantation to treat liver disease.</jats:p>

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