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.
Uygun
Basak E
BE
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Soto-Gutierrez
Alejandro
A
Yagi
Hiroshi
H
Izamis
Maria-Louisa
ML
Guzzardi
Maria A
MA
Shulman
Carley
C
Milwid
Jack
J
Kobayashi
Naoya
N
Tilles
Arno
A
Berthiaume
Francois
F
Hertl
Martin
M
Nahmias
Yaakov
Y
Yarmush
Martin L
ML
Uygun
Korkut
K
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*