Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets.
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.
Ohashi
Kazuo
K
Department of Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan. ohashi@abmes.twmu.ac.jp
Yokoyama
Takashi
T
Yamato
Masayuki
M
Kuge
Hiroyuki
H
Kanehiro
Hiromichi
H
Tsutsumi
Masahiro
M
Amanuma
Toshihiro
T
Iwata
Hiroo
H
Yang
Joseph
J
Okano
Teruo
T
Nakajima
Yoshiyuki
Y
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