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Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix.
Nat Med. 2010 Jul; 16(7):814-20
Didier Samuel, AP-HP Hôpital Paul-Brousse, France. F1000 Gastroenterology & Hepatology
01 Sep 2010 | New Finding
The authors achieved a decellularized liver rat graft with a perfusion decellularization technique; they maintained an acellularized liver matrix that was recellularized with hepatocyte and endothelial cell infusions. The recellularized liver graft was transplanted in an auxiliary position and then was shown to be functional through ex vivo perfusion. This establishes the proof of concept for the use of such recellularized grafts in liver transplantation.
The technique of decellularized and recellularized organs has been developed in the heart and, recently, the lung. This is the first case of decellularized liver being used as a transplantable graft after recellularization. The interest of this technique is its maintenance of the matrix, vessels and the 3D structure of the liver. This new technique should open a new field in liver transplantation and in liver cell culture. The path to a re-engineered human liver is still long but this paper opens up a new era of research.
Acknowledgements: Thanks to Nicolas Moniaux for his help in the evaluation.
Competing interests: No potential interests relevant to this article were reported.
Samuel D: "The authors achieved a decellularized liver rat graft with a perfusion decellularization technique; they maintained..." Evaluation of: [Uygun BE et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010 Jul; 16(7):814-20; doi: 10.1038/nm.2170]. Faculty of 1000, 01 Sep 2010. F1000.com/4916957#eval4847055
Short form
Samuel D: 2010. F1000.com/4916957#eval4847055
Faculty of 1000 evaluations, dissents and comments for [Uygun BE et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010 Jul; 16(7):814-20; doi: 10.1038/nm.2170]. Faculty of 1000, 01 Sep 2010. F1000.com/4916957
Short form
Faculty of 1000: 2010. F1000.com/4916957
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.
DOI: 10.1038/nm.2170
PMID: 20543851
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