Bioreactors for Hybrid Liver Support: Historical Aspects and Novel Designs

ABSTRACT: A novel bioreactor construction has been designed for the utilization of hepatocytes and sinusoidal endothelial cells. The reactor is based on capillaries for hepatocyte aggregate immobilization. Three separate capillary membrane systems, each permitting a different function are woven in order to create a three dimensional network. Cells are perfused via independent capillary membrane compartments. Decentralized oxygen supply and carbon dioxide removal with low gradients are possible. The use of identical parallel units to supply hepatocytes facilitates scale up.

[1]  T. Chang Hybrid artificial cells: microencapsulation of living cells. , 1992, ASAIO journal.

[2]  T. Tsuji,et al.  Glycosaminoglycans partially substitute for proteoglycans in spheroid formation of adult rat hepatocytes in primary culture. , 1988, Cell structure and function.

[3]  M L Yarmush,et al.  Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation , 1992, The Journal of cell biology.

[4]  P. Neuhaus,et al.  Hepatocyte culture between woven capillary networks: a microscopy study. , 1994, Artificial organs.

[5]  A. Sun,et al.  Microencapsulated hepatocytes: an in vitro and in vivo study. , 1987, Biomaterials, artificial cells, and artificial organs.

[6]  Cunningham Jm,et al.  Microcarrier culture of hepatocytes in whole plasma for use in liver support bioreactors. , 1992 .

[7]  G. Belfort,et al.  Enhanced Nutrient Transport in Hollow Fiber Perfusion Bioreactors: A Theoretical Analysis , 1987 .

[8]  J. Driscoll,et al.  Adult Rat Hepatocyte Cultures As The Cellular Component Of An Artificial Hybrid Liver , 1984 .

[9]  A. Shnyra,et al.  Large-scale production and cultivation of hepatocytes on Biosilon microcarriers. , 1990, Artificial organs.

[10]  L. Vīksna,et al.  Temporary organ substitution by hemoperfusion through suspension of active donor hepatocytes in a total complex of intensive therapy in patients with acute hepatic insufficiency. , 1989, Resuscitation.

[11]  J. Stange,et al.  Prolonged biochemical and morphological stability of encapsulated liver cells--a new method. , 1993, Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology.

[12]  F. Schildberg,et al.  Collagen gel immobilization: a useful cell culture technique for long-term metabolic studies on human hepatocytes. , 1994, Xenobiotica; the fate of foreign compounds in biological systems.

[13]  S. Pappas Fulminant hepatic failure and the need for artificial liver support. , 1988, Mayo Clinic proceedings.

[14]  R. Hughes,et al.  Assessment of Bioartificial Liver Support in Acute Liver Failure , 1996, The International journal of artificial organs.

[15]  K. Ishimura,et al.  Importance of cell aggregation for expression of liver functions and regeneration demonstrated with primary cultured hepatocytes , 1993, Journal of cellular physiology.

[16]  F W Schildberg,et al.  Collagen Gel Immobilisation Provides a Suitable Cell Matrix for Long Term Human Hepatocyte Cultures in Hybrid Reactors , 1994, The International journal of artificial organs.

[17]  J. White,et al.  Evaluation of a hepatocyte‐entrapment hollow fiber bioreactor: A potential bioartificial liver , 1993, Biotechnology and bioengineering.

[18]  D. Henne-Bruns Problems and Controversies with Transplantation of Isolated Hepatocytes for Artificial Liver Support , 1992 .

[19]  A. Sun,et al.  Microencapsulated hepatocytes as a bioartificial liver. , 1986, ASAIO transactions.

[20]  B A Solomon,et al.  Biohybrid artificial pancreas: long-term implantation studies in diabetic, pancreatectomized dogs. , 1991, Science.

[21]  Is a clinical application of hybrid liver support systems limited by an initial disorder in cellular amino acid and alpha-keto acid metabolism, rather than by later gradual loss of primary hepatocyte function? , 1996, Transplantation.

[22]  T. Giorgio,et al.  Mass Transfer in a Hollow Fiber Device Used as a Bioartificial Liver , 1993, ASAIO journal.

[23]  N. Marceau,et al.  Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities , 1985, The Journal of cell biology.

[24]  J. Gerlach,et al.  Membranes as Substrates for Hepatocyte Adhesion in Liver Support Bioreactors , 1990, The International journal of artificial organs.

[25]  R. Vanholder,et al.  Bioartificial Pancreas and Liver: A Review , 1991, The International journal of artificial organs.

[26]  Wolf Cf,et al.  Bilirubin conjugation by an artificial liver composed of cultured cells and synthetic capillaries. , 1975 .

[27]  C. Wolf,et al.  Design and Fabrication of a Capillary Cell Culture Chamber for the Study of Convective Flow , 1986, International Journal of Artificial Organs.

[28]  W. Arnaout,et al.  Use of a novel bioartificial liver in a patient with acute liver insufficiency. , 1993, Surgery.

[29]  M. Meissler,et al.  Immunoisolation of Hybrid Liver Support Systems by Semipermeable Membranes , 1997, The International journal of artificial organs.

[30]  K. Asano,et al.  Promotion of spheroid assembly of adult rat hepatocytes by some factor(s) present in the initial 6-hour conditioned medium of the primary culture. , 1991, Pathobiology : journal of immunopathology, molecular and cellular biology.

[31]  B. Eiseman,et al.  Hepatic support with hepatocyte suspensions in a permeable membrane dialyzer. , 1977, Surgery.

[32]  J. Darnell,et al.  Dependence of liver-specific transcription on tissue organization , 1985, Molecular and cellular biology.

[33]  R. Tompkins,et al.  Enzymatic function of alginate immobilized rat hepatocytes , 1988, Biotechnology and bioengineering.

[34]  Leslie E. Blumenson,et al.  Kinetics of gas diffusion in mammalian cell culture systems. II. Theory , 1968 .

[35]  J. Lemasters,et al.  Evidence that activation of Kupffer cells increases oxygen uptake after cold storage. , 1994, Transplantation.

[36]  L. Makowka,et al.  Control of cerebral oedema by total hepatectomy and extracorporeal liver support in fulminant hepatic failure , 1993, The Lancet.

[37]  Achilles A. Demetriou,et al.  Development of a Hybrid Bioartificial Liver , 1993, Annals of surgery.

[38]  J. Encke,et al.  Hepatocyte Culture between Three Dimensionally Arranged Biomatrix-Coated Independent Artificial Capillary Systems and Sinusoidal Endothelial Cell Co-Culture Compartments , 1994, The International journal of artificial organs.

[39]  J. Gerlach,et al.  Development of a Hybrid Liver Support System: A Review , 1996, The International journal of artificial organs.

[40]  K. Asano,et al.  Formation of multicellular spheroids composed of adult rat hepatocytes in dishes with positively charged surfaces and under other nonadherent environments. , 1990, Experimental cell research.

[41]  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.

[42]  C. Cooney,et al.  Model of oxygen transport limitations in hollow fiber bioreactors , 1991, Biotechnology and bioengineering.

[43]  R. Rossaint,et al.  Effect of a Hybrid Liver Support System on Cardiopulmonary Function in Healthy Pigs , 1997, The International journal of artificial organs.

[44]  J. Vienken,et al.  Side Effects of Hybrid Liver Support Therapy: TNF-α Liberation in Pigs, Associated with Extracorporeal Bioreactors , 1993, The International journal of artificial organs.

[45]  R. Tompkins,et al.  Effect of collagen gel configuration on the cytoskeleton in cultured rat hepatocytes. , 1993, Experimental cell research.

[46]  N. Sussman,et al.  Improved liver function following treatment with an extracorporeal liver assist device. , 2008, Artificial organs.

[47]  K. Yagi,et al.  Synthesis and secretion of protein by hepatocytes entrapped within calcium alginate. , 1986, Artificial organs.

[48]  V. Dixit,et al.  Improved function of microencapsulated hepatocytes in a hybrid bioartificial liver support system. , 2008, Artificial organs.

[49]  W. Arnaout,et al.  Development of bioartificial liver: bilirubin conjugation in Gunn rats. , 1990, The Journal of surgical research.

[50]  P Neuhaus,et al.  Improved hepatocyte in vitro maintenance in a culture model with woven multicompartment capillary systems: Electron microscopy studies , 1995, Hepatology.

[51]  M. Rikimaru,et al.  Hybrid bioartificial liver in hepatic failure: preliminary clinical report. , 1987, Surgery.

[52]  P. Gullino,et al.  Cell Culture on Artificial Capillaries: An Approach to Tissue Growth in vitro , 1972, Science.

[53]  V. Dixit Development of a bioartificial liver using isolated hepatocytes. , 1994, Artificial organs.

[54]  P. Neuhaus,et al.  Hepatocyte Aggregate Culture Technique for Bioreactors in Hybrid Liver Support Systems , 1993, The International journal of artificial organs.

[55]  J. White,et al.  Hepatocyte function in a hollow fiber bioreactor: a potential bioartificial liver. , 1992, The Journal of surgical research.

[56]  K. Onodera,et al.  Cellulose microcarrier for high-density culture of hepatocytes. , 1992, Transplantation proceedings.

[57]  T. Tsuji,et al.  Combination of epidermal growth factor and insulin is required for multicellular spheroid formation of rat hepatocytes in primary culture. , 1992, Acta Medica Okayama.

[58]  A. Shnyra,et al.  Bioartificial liver using hepatocytes on biosilon microcarriers: treatment of chemically induced acute hepatic failure in rats. , 1991, Artificial organs.

[59]  U. Christians,et al.  Use of organotypical cultures of primary hepatocytes to analyse drug biotransformation in man and animals. , 1994, Xenobiotica; the fate of foreign compounds in biological systems.

[60]  N. Sussman,et al.  A treatment system for implementing an extracorporeal liver assist device. , 1994, Artificial organs.

[61]  J. Gerlach,et al.  Use of Hepatocytes in Adhesion and Suspension Cultures for Liver Support Bioreactors , 1989, The International journal of artificial organs.

[62]  P. Gullino,et al.  Hormone production by cells grown in vitro on artificial capillaries. , 1974, Experimental cell research.

[63]  S. Nyberg,et al.  Immunoprotection of xenocytes in a hollow fiber bioartificial liver. , 1992, ASAIO journal.

[64]  N Ohshima,et al.  Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel. , 1989, ASAIO transactions.

[65]  R. Tompkins,et al.  Hepatocyte function and extracellular matrix geometry: long‐term culture in a sandwich configuration , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[66]  R. Vanholder,et al.  Artificial Organs - An Overview , 1991, The International journal of artificial organs.

[67]  J. Gerlach,et al.  Endothelial cell seeding on different polyurethanes. , 1989, Artificial organs.

[68]  N. Sussman,et al.  Reversal of fulminant hepatic failure using an extracorporeal liver assist device , 1992, Hepatology.

[69]  K. Yagi,et al.  Characterization of immobilized hepatocytes as liver support. , 1990, Biomaterials, artificial cells, and artificial organs.

[70]  L. Podestá,et al.  A Bioartificial Liver to Treat Severe Acute Liver Failure , 1994, Annals of surgery.

[71]  N. Sussman,et al.  The hepatix extracorporeal liver assist device in the treatment of fulminant hepatic failure. , 1994, ASAIO journal.

[72]  J. Vienken,et al.  Gas supply across membranes in bioreactors for hepatocyte culture. , 1990, Artificial organs.

[73]  E. Hertzberg,et al.  Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures , 1987, The Journal of cell biology.

[74]  J. Encke,et al.  Bioreactor for a larger scale hepatocyte in vitro perfusion. , 1994, Transplantation.

[75]  L.T. Watson,et al.  Analysis of a diffusion‐limited hollow fiber reactor for the measurement of effective substrate diffusivities , 1985, Biotechnology and bioengineering.

[76]  F. Alvarez,et al.  Long-term culture of rat liver cell spheroids in hormonally defined media. , 1990, Experimental cell research.