Induction of in vitro maturation of fetal hepatocytes using 3D PLLA scaffolds for liver tissue engineering :

  • JIANG,Jinlan
    Institute of Frontier Medical Sciences, Jilin University:Institute of Industrial Science, University of Tokyo
  • GUO,Lei
    Division of Artificial Organs & Transplantation, Department of Surgery, Faculty of Medicine, University of Tokyo
  • KOJIMA,Nobuhiko
    Institute of Molecular and Cellular Bioscience, University of Tokyo
  • NARUSE,Katsutoshi
    Division of Artificial Organs & Transplantation, Department of Surgery, Faculty of Medicine, University of Tokyo
  • MAKUUCHI,Masatoshi
    Division of Artificial Organs & Transplantation, Department of Surgery, Faculty of Medicine, University of Tokyo
  • MIYAJIMA,Atsushi
    Institute of Molecular and Cellular Bioscience, University of Tokyo
  • SAKAI,Yasuyuki
    Institute of Industrial Science, University of Tokyo

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抄録

Fetal liver cells are one of the best sources for liver tissue engineering because of their higher ability of proliferation than mature cells in culture. In order to investigate the feasibility of fetal liver cells, the supporting function of poly-L-lactic acid (PLLA) scaffolds for fetal liver cells and the effects of oncostatin M (OSM), nicotinamide (NA) and dimethyl sulfoxide (DMSO) on growth and hepatic differentiation were studied both in vitro and in vivo. After preparing three-dimensional PLLA scaffolds having a welldeveloped open-pore structure, fetal liver cells obtained from mouse embryos were inoculated in the scaffolds. Cells were cultured in Williams' E medium with or without OSM, NA and DMSO for 30 days. Changes in cell number, some liver-specific functions, and cellular morphology were studied both at day 15 and day 30. Then, the scaffolds which were cultured in Williams' E medium with OSM, NA and DMSO for 15 days were implanted into the peritoneal cavity of 70% hepatotectomized mice. The histological and liver-specific function changes of engrafted fetal liver cells in the PLLA scaffolds after 15 and 30 days were observed. Our results showed that three-dimensional PLLA scaffold is a good support material for the cultivation of fetal liver cells; OSM, NA and DMSO remarkably stimulated maturation of hepatic parenchymal cells both in vitro and in vivo in terms of morphology and liver-specific functions. Therefore, our engineered liver tissue based on three-dimensional PLLA scaffolds and in vitro propagated hepatocyte progenitors is feasible for in vivo transplantation, and it has a potential to resolve the deficiency in the source of cells for liver tissue engineering.

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