Summary
Hybrid artificial liver systems are being developed as extracorporeal temporary liver support therapy. Here, an overview is given with emphasis on hepatocyte culture models for bioreactors, in vitro studies, animal studies and the clinical application of hybrid liver support systems. In vitro studies show long term external metabolic functions of primary isolated hepatocytes in bioreactors. These systems are capable of supporting essential liver functions. Animal experiments show the possibility of upscaling the bioreactors for clinical treatment. Since there is no reliable animal model for investigations on the treatment of acute liver failure, the promising results of these studies have limited relevance. The small number of clinical studies are not sufficient to give statements about a clinical improvement of therapy of acute liver failure. Although important progress has been made in the development of the systems, multiple different hepatocyte culture models and bioreactor constructions are discussed in the literature, indicating competition in this field of medical research.
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References
Trey C, Davidson LS.,1970, In: Popper H, Schaffner F (eds): Progress in liver diseases. Grune and Stratton, New York: p. 282.
European association for the study of the liver, 1987, Randomized trial of steroid therapy in acute liver failure. Gut 20:20–23.
O’Grady JG, Gimson AES, O’Brien CJ et al., 1988, Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 94:1186–1192.
Ring-Larsen H, Palazzo V., 1985, Renal failure in fulminant hepatic failure and terminal cirrhosis.Gut 22:585–591.
Jones EA, Schaefer DF. Fulminant hepatic failure. In: Zakim D, Boyer TD, eds. Hepatology.Philadelphia: Saunders, 1990:460–475.
Wolf CFW, Munkelt BE., 1975, Bilirubin conjugation by an artificial liver composed of cultured cells and synthetic capillaries. ASAIO Transactions 21:16–27.
Sussman NL, Chong MG, Koussayer T, He DE, Shang TA, Hartwell H, Whisennhalld, Kelly JH,1992, Reversal of fulminant hepatic failure using an extracorporeal liver assist device, Hepatology 16:60–65.
Howard RB, Christensen AK, Gibbs FA und Pesch LA., 1967, The Enzymatic Preparation of Isolated Intact Parenchymal Cells from Rat Liver. The Journal of Cell Biology 35:675–684.
Berry MN und Friend DS, 1969, High-Yield Preparation of Isolated Rat Liver Parenchymal Cells.J.Cell Biol. 43:506–520.
Berry MN, 1974, High-Yield Preparation of Morphologically Intact Isolated Parenchymal Cells from Rat Liver. In “Methods in Enzymology” (S.Fleischer and L.Packer,eds.), Volume 32, pp.625–632, Academic Press, New York, 625–632.
Seglen PO., 1972, Preparation of Rat Liver Cells: I. Effect of calcium on enzymatic dispersion in perfused liver. Experimental Cell Research 74:450–454.
Seglen PO., 1973, Preparation of Rat Liver Cells: III. Enzymatic requirements for tissue dispersion, Experimental Cell Research 82:391–398.
Gerlach J, Brombacher J, Courtney JM, Neuhaus P., 1993, Nonenzymatic versus enzymatic hepatocyte isolation from pig livers for larger scale investigation of liver cell perfusion systems, Int. J. Artificial Organs. 16:677–681.
Gerlach J, Klöppel K, Schön MR, Brombacher J, Courtney JM, Unger J, Neuhaus P., 1993,Comparison of pig hepatocyte isolation using intraoperative perfusion without warm iscemia and isolation of cells from abattoir organs after warm iscemia, Artificial Organs. 17:950–953.
Gerlach J, Brombacher J, Klöppel K, Schnoy N, Neuhaus P., 1994, Comparison of four methods for mass hepatocyte isolation from pig and human livers, Transplantation. 57:1318–1322.
Gerlach J, Grehn S, Neuhaus P., 1993, Endothelial cell kinetics after anoxia and hypothermia in preservation solutions as indicator for endothelial repair. Transpl. Proc. 25/11:1593–1594.
Gjessing R, Seglen PO, 1980, Adsorption, simple binding and complex binding of rat hepatocytes to various in vitro substrata, Exp. Cell Res. 129:239–240.
Rubin K, Golderg A, Höök M, Öbrink B., 1978, Adhesion of rat hepatocytes to collagen, Exp.Cell Res. 117:127–135.
Roijkind M, Gatmaitan Z, Mackensen S, Giambrone MA, Ponce P, Reid LM., 1980, Connective tissue Biomatrix: Its isolation and utilisation for long term cultures of normal rat hepatocytes, J Cell Biol 87:225–263.
Enat R, Jefferson DM, Ruiz-Opazo N, Gatmaitan Z, Leinwand LA, Reid L., 1984, Hepatocyte proliferation in vitro: its dependence on the use of hormonally defined medium and substrata of extracellular matrix, Proc Natl Acad Sci USA, 81:1411–1415.
Bissel DM, Arenson DM, Maher JJ , Roll FJ., 1987, Support of cultured hepatocytes by a lamininrich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver, J Clin Invest 79:801–812.
Guguen-Guillouzo C, Clement B, Baffet G, Beaumont C, Morel-Chaney E, Glaise D, Guillouzo A., 1983, Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver specific cell type, Exp Cell Res. 143:47–54.
Clement B, Gugen-Guillouzo C, Ca;.ipion JP., 1984, Long term co-cultures of adult human hepatocytes with rat liver epithelial cells: Modulation of albumin secretion and accumulation of extracellular meterial, Hepatology 4:373–380.
Leffert HL. Koch KS., 1982, Hepatocyte growth regulation by hormones in chemically defined media: A two signal hypothesis. In: Sato GH, Sirbasku AA, eds. Growth of cells in hormonally defined media. Cold Spring Harbour NY, Cold Spring Laboratory: 597–613.
Koch KS, Lu X, Brenner DA., 1990, Mitogens and hepatocyte growth control in vivo and in vitro.In Vitro Cell Dev Biol 26:1011–1022.
Shnyra A, Bocharow A, Bochkova N, Spirov V., 1991, Bioartificial liver using hepatocytes on biosilon microcarriers: treatment of chemically induced acute hepatic failure in rats, Artif. Org. 15:189–197.
Yanagi K, Ookawa K, Mizuno S, Ohshima N., 1989, Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel. ASAIO Transactions 35:570– 572.
Dunn JCY, Yarmush ML, Koebe HG, Tompkins RG., 1989, Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB 3:174–177.
Nyberg SL, Shatford RA, Peshwa MV, White JG, Cerra FB, Hu WS,I993, Evaluation of a hepatocyte entrapment hollow fiber bioreactor: a potential artificial liver. Biot. Bioeng. 4:194– 203.
Knazek, RA, PM. Gullino, PO. Kohler, RL. Dedrick, 1972, Science 178:65–67.
Knazek, R. A., P. O. Kohler, P. M. Gullino, 1979, Exp. Cell Res. 84:251–254.
Rozga J, Williams F, Ro MS, Neuzil DF, Giorgio TD, Backfisch G, Moscioni AD, Hakim R,Demetriou AA, 1993, Development of a bioartificial liver: Properties and function of a hollow-fiber module inoculated with liver cells, Hepatology 17:258–265
Jauregiou HO, Naik S, Solomon BA, Duffy RL, Lipski M, Galetti PM, 1983, Attachment of adult rat hepatocytes to modified Amicon XM-50 membranes. ASAIO Transactions 19:698–702.
Shatford RA, Nyberg SL, Payne WD, Hu WS, Cerra FB,1991, A hepatocyte bioreactor as a potential bioartificial liver: Demonstration of prolonged tissue-specific functions. In: Gere MA: Surgical Forum XLII, Chicago:54–56.
Yanagi K, Ookawa K, Mizuno S, Ohshima N, 1989, Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel. ASAIO Transactions 35/3:570– 572.
Takabatake H, Koide N, Tsuji T, 1991, Encapsulated multicellular speroids of rat hepatocytes produce albumin and urea in a spouted bed circulating culture system, Artif. Org. 15:474–480.
Koide N, Sakagucci K, Koide Y., 1990, Formation of multicellular spheroids composed of adult rat hepatocytes in dishes with positive charged surfaces and under other nonadherent environments. Exp. Cell Res. 186:227–235.
Berry MN, Edwards AM, Banit GJ., 1991, Isolated hepatocytes preparation, properties and applications. In: Burdon RH, van Knippenberg PH eds. Laboratory techniques in biochemistry and molecular biology. Amsterdam: Elsevier.
Kelly JH, Koussayer T, He DE, Chong MG, Shang TA, Hartwell H, Whisennand, Sussman NL,1992, An improved model of acetaminophen-induced fulminant hepatic failure in dogs. Hepatology 15:329–335.
Jauregui HO, 1991, Treatment of hepatic insufficiency based on cellular therapies. Artif. Org.14:321–326.
Filipponi F, Fabbri LP, Marsili M, Falcini F. Benassai C. Nucera M, Romagnoli P., 1991, A new surgical model of acute liver failure in the pig: Experimental procedure and analysis of liver injury. Eur. Surg. Res. 23:58–64.
Uchino J, Tsuburaya T, Kumagai F, Hase T, Hamada T, Komai T, Funatsu A, Hashimura E,Nakamura K, Kon T, 1988, “A hybrid bioartificial liver composed of multiplated hepatocyte monolayers”, ASAIO Transactions 34:972–977.
Arnaout WS, Moscioni AD, Barbour RL, Demetriou AA., 1990, Development of bioartificial liver:Bilirubin conjugation in gunn rats. Journal of Surgical Research 48/4:379–382.
Demetriou A. et al., 1986, New method of hepatocyte transplantation and extracorporal liver support. Annals of Surgery, Vol. 204:259–271.
Gerlach J, Jörres A, Vienken J, Gahl GM, and Neuhaus P., 1993, Side effects of hybrid liver support therapy: TNF liberation in pigs, connected with extracorporeal bioreactors. Int. J. Artif. Org. 16:604–608.
Matsumura KN, Guevara GR, Huston H, Hamilton WL, Rilíimaru M, Yamasaki G, Matsumura MS., 1987, “Hybrid bioartificial liver in hepatic failure: Preliminary clinical report” Surgery 101, No.1:99–103.
Margulis MS, Erukhimov EA, Andreiman LA, Kuznetsov KA, Viksna LM, Kuznetsov AI,Devyatov W., 1990, Hemoperfusion through suspension of cryopreserved hepatocytes in a treatment of patients with acute liver failure. Research in Surgery 2:99–102.
Margulis MS, Erukhimov EA, Andreiman LA., 1989, Temporary organ substitution by hemoperfusion through suspension of active donor hepatocytes in a total complex of intensive therapy in patients with acute hepatic insufficiency. Resuscitation 18:85–94.
Neuzil D, Rozga J, Moscioni AD, Ro MS, Hakim R, Arnaout WS, Demetriou AA., 1993, Use of a novel bioartificial liver in a patient with acute liver insufficiency. Surgery 113(3):340–3.
Sussman NL, Kelly JH., 1993, Improved liver function following treatment with an extracorporal liver assist device. Artif-Organs 17(1):27–30.
Gerlach J, Stoll P, Schnoy N, Bücherl ESB., 1990, Membranes as substrate for hepatocyte adhesion in liver support bioreactors. Int. J. Artif. Org. 13/1:436–441.
Hynda KK, Mc Garvey ML, Liotta LA, Robbey PG, Tryggvason K, Martin GR., 1982, Isolation and characterisation of type IV procollagen, laminin and heparan sulfate proteoglycans from the EHS sarcoma. Biochemistry 21:6188–93.
Gerlach J, Schnoy N, Smith MD, Neuhaus P., 1994, Hepatocyte culture between woven capillary networks -a microscopy study. Int. Artif. Org. 18:226–230.
Gerlach J, Klöppel K, Stoll P, Vienken J, Müller Ch, Schauwecker HH., 1990, Gas supply across membranes in liver support bioreactors. Artif. Org. 14:328–333.
Gerlach J, Schauwecker HH, Klöppel K, Tauber R, Müller Ch, and Bücherl ES., 1989, Use of hepatocytes in adhesion and suspension cultures for liver support bioreactors. Int. J. Artif. Org. 12:788–793.
Gerlach J, Schauwecker HH, Hennig E, Bücherl ES., 1989, Endothelial cell seeding on different polyurethanes. Artif Org 13:144–147.
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Gerlach, J.C. (1994). Use of Hepatocyte Cultures for Liver Support Bioreactors. In: Felipo, V., Grisolia, S. (eds) Hepatic Encephalopathy, Hyperammonemia, and Ammonia Toxicity. Advances in Experimental Medicine and Biology, vol 368. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1989-8_18
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DOI: https://doi.org/10.1007/978-1-4615-1989-8_18
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