BACKGROUND: Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. MATERIALS AND METHODS: Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GalN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. RESULTS: Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). CONCLUSIONS: This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF.
BACKGROUND:Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. MATERIALS AND METHODS: Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GalN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. RESULTS: Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). CONCLUSIONS: This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF.
Authors: Andreas K Nussler; Katrin Zeilinger; Lilianna Schyschka; Sabrina Ehnert; Jörg C Gerlach; Xueying Yan; Serene M L Lee; Maren Ilowski; Wolfgang E Thasler; Thomas S Weiss Journal: J Mater Sci Mater Med Date: 2011-04-03 Impact factor: 3.896
Authors: Masahiro Shinoda; Arno W Tilles; Go Wakabayashi; Atsushi Takayanagi; Hirohisa Harada; Hideaki Obara; Kazuhiro Suganuma; François Berthiaume; Motohide Shimazu; Nobuyoshi Shimizu; Masaki Kitajima; Ronald G Tompkins; Mehmet Toner; Martin L Yarmush Journal: Tissue Eng Date: 2006-05
Authors: Masahiro Shinoda; Arno W Tilles; Naoya Kobayashi; Go Wakabayashi; Atsushi Takayanagi; Toshinori Totsugawa; Hirohisa Harada; Hideaki Obara; Kazuhiro Suganuma; François Berthiaume; Motohide Shimazu; Nobuyoshi Shimizu; Noriaki Tanaka; Masaki Kitajima; Ronald G Tompkins; Mehmet Toner; Martin L Yarmush Journal: J Surg Res Date: 2006-11-01 Impact factor: 2.192
Authors: Hiroshi Yagi; Biju Parekkadan; Kazuhiro Suganuma; Alejandro Soto-Gutierrez; Ronald G Tompkins; Arno W Tilles; Martin L Yarmush Journal: Tissue Eng Part A Date: 2009-11 Impact factor: 3.845