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Application of whole-organ tissue engineering in hepatology

Nature Reviews Gastroenterology & Hepatology volume 9, pages 738–744 (2012)Cite this article

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Abstract

Initially hailed as the ultimate solution to organ failure, engineering of vascularized tissues such as the liver has stalled because of the need for a well-structured circulatory system that can maintain the cells seeded inside the construct. A new approach has evolved to overcome this obstacle. Whole-organ decellularization is a method that retains most of the native vascular structures of the organ, providing microcirculatory support and structure, which can be anastomosed with the recipient circulation. The technique was first applied to the heart and then adapted for the liver. Several studies have shown that cells can be eliminated, the extracellular matrix and vasculature are reasonably preserved and, after repopulation with hepatocytes, these grafts can perform hepatic functions in vitro and in vivo. Progress is rapidly being made as researchers are addressing several key challenges to whole-organ tissue engineering, such as ensuring correct cell distribution, nonparenchymal cell seeding, blood compatibility, immunological concerns, and the source of cells and matrices.

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Figure 1: Principles of whole-liver engineering.

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Acknowledgements

Funding from the National Institutes of Health (R01DK084053, R01DK096075R01, K99DK088962), National Science Foundation (CBET 0853569) and the Shriners Hospitals for Children are gratefully acknowledged.

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  1. Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children, 51 Blossom Street, Boston, MA 02114, USA,

    Basak E. Uygun, Martin L. Yarmush & Korkut Uygun

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All authors contributed equally to all aspects of the article.

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Correspondence to Korkut Uygun.

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B. E. Uygun, M. L. Yarmush and K. Uygun are patent applicants for Massachusetts General Hospital, Boston, MA, USA. The patent application relates to hepatic tissue engineering processes (application number WO2011002926).

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Uygun, B., Yarmush, M. & Uygun, K. Application of whole-organ tissue engineering in hepatology. Nat Rev Gastroenterol Hepatol 9, 738–744 (2012). https://doi.org/10.1038/nrgastro.2012.140

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