Human-scale whole-organ bioengineering for liver transplantation: A regenerative medicine approach

Hiroshi Yagi, Ken Fukumitsu, Kazumasa Fukuda, Minoru Kitago, Masahiro Shinoda, Hideaki Obara, Osamu Itano, Shigeyuki Kawachi, Minoru Tanabe, Gina M. Coudriet, Jon D. Piganelli, Thomas W. Gilbert, Alejandro Soto-Gutierrez, Yuukou Kitagawa

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)231-242
Number of pages12
JournalCell Transplantation
Volume22
Issue number2
DOIs
Publication statusPublished - 2013

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Bioengineering
Regenerative Medicine
Liver
Liver Transplantation
Swine
Transplantation
Liver Regeneration
Organ Culture Techniques
Liver Failure
Treatment Failure
Bile
Extracellular Matrix
Liver Diseases
Drainage
Hepatocytes
Rodentia
Transplantation (surgical)
Perfusion
Transplants
Scaffolds (biology)

Keywords

  • Bile duct
  • Bioengineering in organ transplantation
  • Decellularization
  • Liver tissue engineering
  • Porcine liver
  • Regenerative medicine
  • Whole-organ scaffold

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Human-scale whole-organ bioengineering for liver transplantation : A regenerative medicine approach. / Yagi, Hiroshi; Fukumitsu, Ken; Fukuda, Kazumasa; Kitago, Minoru; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kawachi, Shigeyuki; Tanabe, Minoru; Coudriet, Gina M.; Piganelli, Jon D.; Gilbert, Thomas W.; Soto-Gutierrez, Alejandro; Kitagawa, Yuukou.

In: Cell Transplantation, Vol. 22, No. 2, 2013, p. 231-242.

Research output: Contribution to journalArticle

Yagi, H, Fukumitsu, K, Fukuda, K, Kitago, M, Shinoda, M, Obara, H, Itano, O, Kawachi, S, Tanabe, M, Coudriet, GM, Piganelli, JD, Gilbert, TW, Soto-Gutierrez, A & Kitagawa, Y 2013, 'Human-scale whole-organ bioengineering for liver transplantation: A regenerative medicine approach', Cell Transplantation, vol. 22, no. 2, pp. 231-242. https://doi.org/10.3727/096368912X654939
Yagi, Hiroshi ; Fukumitsu, Ken ; Fukuda, Kazumasa ; Kitago, Minoru ; Shinoda, Masahiro ; Obara, Hideaki ; Itano, Osamu ; Kawachi, Shigeyuki ; Tanabe, Minoru ; Coudriet, Gina M. ; Piganelli, Jon D. ; Gilbert, Thomas W. ; Soto-Gutierrez, Alejandro ; Kitagawa, Yuukou. / Human-scale whole-organ bioengineering for liver transplantation : A regenerative medicine approach. In: Cell Transplantation. 2013 ; Vol. 22, No. 2. pp. 231-242.
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