title: Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets.
abstract: Hepatic tissue engineering using primary hepatocytes has been considered a valuable new therapeutic modality for several classes of liver diseases. Recent progress in the development of clinically feasible liver tissue engineering approaches, however, has been hampered mainly by insufficient cell-to-cell contact of the engrafted hepatocytes. We developed a method to engineer a uniformly continuous sheet of hepatic tissue using isolated primary hepatocytes cultured on temperature-responsive surfaces. Sheets of hepatic tissue transplanted into the subcutaneous space resulted in efficient engraftment to the surrounding cells, with the formation of two-dimensional hepatic tissues that stably persisted for longer than 200 d. The engineered hepatic tissues also showed several characteristics of liver-specific functionality. Additionally, when the hepatic tissue sheets were layered in vivo, three-dimensional miniature liver systems having persistent survivability could be also engineered. This technology for liver tissue engineering is simple, minimally invasive and free of potentially immunogenic biodegradable scaffolds.
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan. ohashi@abmes.twmu.ac.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuge
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kanehiro
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Amanuma
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
authors.forename: Joseph
authors.initials: J
authors.lastname: Yang
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D006085:Graft Survival; D022781:Hepatocytes / Q000166:cytology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023822:Tissue Engineering / Q000379:methods*; D016378:Tissue Transplantation