Liver regeneration using a hybrid artificial liver support system.

We have developed two types of hybrid artificial liver support system (HALSS) that use hepatocyte organoid culture: (1) a PUF-HALSS comprising an artificial liver module using polyurethane foam (PUF), in which hepatocytes form spheroids in its pores, and maintained liver-specific functions for at least ten days in vitro; (2) an LLS-HALSS that uses a liver lobule-like structure (LLS) module containing hollow fibers with a microregular arrangement in which hepatocytes in the extra-fiber space of the module form the organoids by centrifugation that maintain liver-specific functions for at least two months in vitro. In preclinical experiments, a PUF-HALSS was applied to a pig having liver failure. To evaluate the effect of liver regeneration, a PUF- and an LLS-HALSS were applied to a rat having reversible hepatic failure. Each HALSS was effective in supporting liver function, stabilization of general conditions and recovery from liver failure state. These results indicate that these HALSS may be useful to treat liver failure patients until liver transplantation or until regeneration of the native liver.

[1]  K. Asano,et al.  Continued high albumin production by multicellular spheroids of adult rat hepatocytes formed in the presence of liver-derived proteoglycans. , 1989, Biochemical and biophysical research communications.

[2]  M. Suzuki,et al.  Large-Scale Preparation and Function of Porcine Hepatocyte Spheroids , 1996, The International journal of artificial organs.

[3]  W. Heneine,et al.  Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. , 1999, Science.

[4]  M. Shimada,et al.  Mass Preparation of Primary Porcine Hepatocytes and the Design of a Hybrid Artificial Liver Module using Spheroid Culture for a Clinical Trial , 2001, The International journal of artificial organs.

[5]  H. Mizumoto,et al.  Recovery of Rats with Fulminant Hepatic Failure by using a Hybrid Artificial Liver Support System with Polyurethane Foam/Rat Hepatocyte Spheroids , 2002, The International journal of artificial organs.

[6]  M. Löhr,et al.  Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support. , 1999, Artificial organs.

[7]  A. Demetriou,et al.  Treatment of Severe Liver Failure with a Bioartificial Liver a , 1997, Annals of the New York Academy of Sciences.

[8]  K. Sugimachi,et al.  Formation of porcine hepatocyte spherical multicellular aggregates (spheroids) and analysis of drug metabolic functions , 2004, Cytotechnology.

[9]  T. Tani,et al.  Bioartificial liver support system using porcine hepatocytes entrapped in a three-dimensional hollow fiber module with collagen gel: An evaluation in the swine acute liver failure model. , 1999, Artificial organs.

[10]  S. Ash,et al.  Cytokines and endotoxin removal by sorbents and its application in push-pull sorbent-based pheresis: the BioLogic-DTPF System. , 1999, Artificial organs.

[11]  N. Sussman,et al.  The Hepatix extracorporeal liver assist device: initial clinical experience. , 1994, Artificial organs.

[12]  S. Matsubara,et al.  Combination of plasma exchange and continuous hemofiltration as temporary metabolic support for patients with acute liver failure. , 1994, Artificial organs.

[13]  G. Mazariegos,et al.  Safety Observations in Phase I Clinical Evaluation of the Excorp Medical Bioartificial Liver Support System after the First Four Patients , 2001, ASAIO journal.

[14]  H. Mizumoto,et al.  Formation of a spherical multicellular aggregate (spheroid) of animal cells in the pores of polyurethane foam as a cell culture substratum and its application to a hybrid artificial liver. , 1998, Journal of biomaterials science. Polymer edition.

[15]  K. Sugimachi,et al.  Conditions Required for a Hybrid Artificial Liver Support System using a PUF/Hepatocyte-Spheroid Packed-Bed Module and it's use in Dogs with Liver Failure , 2000, The International journal of artificial organs.

[16]  K Sugimachi,et al.  Hybrid artificial liver using hepatocyte organoid culture. , 2001, Artificial organs.

[17]  K Sugimachi,et al.  Efficacy of a Polyurethane Foam/Spheroid Artificial Liver by Using Human Hepatoblastoma Cell Line (Hep G2) , 2003, Cell transplantation.

[18]  Y. Ikada,et al.  In vitro evaluation of metabolic functions of a bioartificial liver. , 1999, ASAIO journal.

[19]  K Sugimachi,et al.  Evaluation of a hybrid artificial liver using a polyurethane foam packed-Bed culture system in dogs. , 1999, The Journal of surgical research.

[20]  I M Sauer,et al.  Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report , 2002, The International journal of artificial organs.

[21]  M. Shimada,et al.  Development of a Hybrid Artificial Liver Using Polyurethane Foam / Hepatocyte Spheroid Culture in a Preclinical Pig Experiment , 2002, The International journal of artificial organs.

[22]  K. Nakazawa,et al.  Novel hybrid Artificial Liver using Hepatocyte Organoids , 2002, The International journal of artificial organs.

[23]  Y. Sakai,et al.  Comparisons of Porcine Hepatocyte Spheroids and Single Hepatocytes in the Non-Woven Fabric Bioartificial Liver Module , 1996, The International journal of artificial organs.

[24]  Kohji Nakazawa,et al.  Hepatocyte Spheroids in Polyurethane Foams: Functional Analysis and Application for a Hybrid Artificial Liver , 1998 .

[25]  N Ohshima,et al.  Improvement of metabolic performance of hepatocytes cultured in vitro in a packed-bed reactor for use as a bioartificial liver. , 1998, ASAIO journal.