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


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.

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Figure 1: Decellularization of ischemic rat livers.
Figure 2: DLM retains intact lobular structure and vascular bed.
Figure 3: Repopulation of rat DLM with adult rat hepatocytes.
Figure 4: Hepatic function of the recellularized liver graft in vitro.
Figure 5: Transplantation of the recellularized liver graft.


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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 CBET-0853569 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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K.U. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. B.E.U., A.S.-G., H.Y. and K.U., study concept and design; B.E.U., A.S.-G., H.Y., M.A.G., acquisition of data; B.E.U., A.S.-G., Y.N. and K.U., analysis and interpretation of data; M.-L.I., C.S. and B.E.U., rat liver harvest, decellularization and hepatocyte isolation; J.M. and B.E.U., design and construction of the recellularized liver chamber; B.E.U., A.S.-G., H.Y. and M.A.G., recellularization; A.S.-G. and H.Y., histology and transplantation studies; B.E.U., A.S.-G., H.Y. and K.U., drafting of the manuscript; B.E.U., A.S.-G., H.Y., M.L.Y., Y.N., A.T., F.B., M.H., N.K. and K.U., critical revision of the manuscript for intellectual content; B.E.U. and K.U., statistical analysis; M.L.Y., K.U. and A.S.-G., obtained funding; M.-L.I., C.S., J.M., Y.N., A.T. and F.B., administrative, technical or material support. All authors contributed to the preparation of the report.

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Correspondence to Korkut Uygun.

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The authors declare no competing financial interests.

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Supplementary Tables 1 and 2, Supplementary Figures 1–5 and Supplementary Methods (PDF 4275 kb)

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Uygun, B., Soto-Gutierrez, A., Yagi, H. et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 16, 814–820 (2010).

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