Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix

Basak E. Uygun, Alejandro Soto-Gutierrez, Hiroshi Yagi, Maria Louisa Izamis, Maria A. Guzzardi, Carley Shulman, Jack Milwid, Naoya Kobayashi, Arno Tilles, Francois Berthiaume, Martin Hertl, Yaakov Nahmias, Martin L. Yarmush, Korkut Uygun

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Abstract

Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.

Original languageEnglish
Pages (from-to)814-820
Number of pages7
JournalNature Medicine
Volume16
Issue number7
DOIs
Publication statusPublished - 2010 Jul

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Uygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M. L., Guzzardi, M. A., Shulman, C., Milwid, J., Kobayashi, N., Tilles, A., Berthiaume, F., Hertl, M., Nahmias, Y., Yarmush, M. L., & Uygun, K. (2010). Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nature Medicine, 16(7), 814-820. https://doi.org/10.1038/nm.2170