Technical Report abstract


Nature Medicine 13, 880 - 885 (2007)
Published online: 17 June 2007 | doi:10.1038/nm1576

Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets

Kazuo Ohashi1,6, Takashi Yokoyama1, Masayuki Yamato2, Hiroyuki Kuge1, Hiromichi Kanehiro1, Masahiro Tsutsumi3, Toshihiro Amanuma4, Hiroo Iwata5, Joseph Yang2, Teruo Okano2 & Yoshiyuki Nakajima1


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.

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  1. Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
  2. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
  3. Department of Pathology, Saiseikai Chuwa Hospital, 323 Abe, Sakurai, Nara 633-0054, Japan.
  4. Nihon Noyaku, Co. Ltd., 345 Oymada-cho, Kawachinagano, Osaka 586-0094, Japan.
  5. Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
  6. Present address: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Correspondence to: Kazuo Ohashi1,6 e-mail: ohashi@abmes.twmu.ac.jp



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