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

Research output: Contribution to journalArticlepeer-review

1149 Scopus citations

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 languageAmerican English
Pages (from-to)814-820
Number of pages7
JournalNature Medicine
Volume16
Issue number7
DOIs
StatePublished - Jul 2010

Bibliographical note

Funding Information:
This work was supported by grants from the US National Institutes of Health, R01DK59766 and R01DK084053 to M.L.Y., K99/R00 DK080942 to K.U. and K99DK083556 to A.S.G., and US National Science Foundation CBET0853569 to K.U. We thank the support of the Shriners Hospitals for Children to B.E.U. (grant no. 8503), the American Liver Foundation to A.S.G. and Massachusetts General Hospital Junior Faculty Grant to K.U. and the Shriners Hospitals for Children. We would like to thank A. Vitalo, C. Calhoun and B. Crowther for technical support.

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