title: Human-scale whole-organ bioengineering for liver transplantation: a regenerative medicine approach.
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.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Ken
authors.initials: K
authors.lastname: Fukumitsu
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fukuda
authors.forename: Minoru
authors.initials: M
authors.lastname: Kitago
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinoda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obara
authors.forename: Osamu
authors.initials: O
authors.lastname: Itano
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawachi
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.forename: Gina M
authors.initials: GM
authors.lastname: Coudriet
authors.forename: Jon D
authors.initials: JD
authors.lastname: Piganelli
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gilbert
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutierrez
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D044968:Regenerative Medicine / Q000379:methods*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*