title: Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix.
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.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Basak E
authors.initials: BE
authors.lastname: Uygun
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutierrez
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Maria-Louisa
authors.initials: ML
authors.lastname: Izamis
authors.forename: Maria A
authors.initials: MA
authors.lastname: Guzzardi
authors.forename: Carley
authors.initials: C
authors.lastname: Shulman
authors.forename: Jack
authors.initials: J
authors.lastname: Milwid
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Arno
authors.initials: A
authors.lastname: Tilles
authors.forename: Francois
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Martin
authors.initials: M
authors.lastname: Hertl
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Nahmias
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology; D008102:Liver Circulation; D016031:Liver Transplantation / Q000379:methods*; D009926:Organ Preservation; D010477:Perfusion; D011169:Portal Vein; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*