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

Authors :
Uygun BE
Soto-Gutierrez A
Yagi H
Izamis ML
Guzzardi MA
Shulman C
Milwid J
Kobayashi N
Tilles A
Berthiaume F
Hertl M
Nahmias Y
Yarmush ML
Uygun K
Source :
Nature medicine [Nat Med] 2010 Jul; Vol. 16 (7), pp. 814-20. Date of Electronic Publication: 2010 Jun 13.
Publication Year :
2010

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.

Details

Language :
English
ISSN :
1546-170X
Volume :
16
Issue :
7
Database :
MEDLINE
Journal :
Nature medicine
Publication Type :
Academic Journal
Accession number :
20543851
Full Text :
https://doi.org/10.1038/nm.2170