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Fabrication of acellular scaffolds by cryo-chemical decellulaurization of the whole liver for mesenchymal stem cell-based functional hepatic engineering

  • O. Lee
    Affiliations
    1Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan

    2Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
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  • W. Jiang
    Affiliations
    1Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan

    3Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan
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      Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a novel cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and creates acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs.
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