Skip to main content

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 368))

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Trey C, Davidson LS.,1970, In: Popper H, Schaffner F (eds): Progress in liver diseases. Grune and Stratton, New York: p. 282.

    Google Scholar 

  2. European association for the study of the liver, 1987, Randomized trial of steroid therapy in acute liver failure. Gut 20:20–23.

    Google Scholar 

  3. 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.

    PubMed  Google Scholar 

  4. Ring-Larsen H, Palazzo V., 1985, Renal failure in fulminant hepatic failure and terminal cirrhosis.Gut 22:585–591.

    Article  Google Scholar 

  5. Jones EA, Schaefer DF. Fulminant hepatic failure. In: Zakim D, Boyer TD, eds. Hepatology.Philadelphia: Saunders, 1990:460–475.

    Google Scholar 

  6. Wolf CFW, Munkelt BE., 1975, Bilirubin conjugation by an artificial liver composed of cultured cells and synthetic capillaries. ASAIO Transactions 21:16–27.

    CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. Berry MN und Friend DS, 1969, High-Yield Preparation of Isolated Rat Liver Parenchymal Cells.J.Cell Biol. 43:506–520.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Google Scholar 

  11. Seglen PO., 1972, Preparation of Rat Liver Cells: I. Effect of calcium on enzymatic dispersion in perfused liver. Experimental Cell Research 74:450–454.

    Article  PubMed  CAS  Google Scholar 

  12. Seglen PO., 1973, Preparation of Rat Liver Cells: III. Enzymatic requirements for tissue dispersion, Experimental Cell Research 82:391–398.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. Rubin K, Golderg A, Höök M, Öbrink B., 1978, Adhesion of rat hepatocytes to collagen, Exp.Cell Res. 117:127–135.

    Article  Google Scholar 

  19. 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.

    Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    CAS  Google Scholar 

  29. 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.

    Google Scholar 

  30. Knazek, RA, PM. Gullino, PO. Kohler, RL. Dedrick, 1972, Science 178:65–67.

    Article  PubMed  CAS  Google Scholar 

  31. Knazek, R. A., P. O. Kohler, P. M. Gullino, 1979, Exp. Cell Res. 84:251–254.

    Article  Google Scholar 

  32. 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

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Google Scholar 

  34. 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.

    Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    CAS  Google Scholar 

  37. 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.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

  40. Jauregui HO, 1991, Treatment of hepatic insufficiency based on cellular therapies. Artif. Org.14:321–326.

    CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. 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.

    PubMed  CAS  Google Scholar 

  43. 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.

    Article  PubMed  CAS  Google Scholar 

  44. Demetriou A. et al., 1986, New method of hepatocyte transplantation and extracorporal liver support. Annals of Surgery, Vol. 204:259–271.

    Article  PubMed  CAS  Google Scholar 

  45. 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.

    CAS  Google Scholar 

  46. 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.

    PubMed  CAS  Google Scholar 

  47. 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.

    Google Scholar 

  48. 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.

    Article  PubMed  CAS  Google Scholar 

  49. 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.

    PubMed  CAS  Google Scholar 

  50. Sussman NL, Kelly JH., 1993, Improved liver function following treatment with an extracorporal liver assist device. Artif-Organs 17(1):27–30.

    Article  PubMed  CAS  Google Scholar 

  51. 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.

    CAS  Google Scholar 

  52. 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.

    Article  Google Scholar 

  53. Gerlach J, Schnoy N, Smith MD, Neuhaus P., 1994, Hepatocyte culture between woven capillary networks -a microscopy study. Int. Artif. Org. 18:226–230.

    Article  CAS  Google Scholar 

  54. 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.

    Article  CAS  Google Scholar 

  55. 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.

    CAS  Google Scholar 

  56. Gerlach J, Schauwecker HH, Hennig E, Bücherl ES., 1989, Endothelial cell seeding on different polyurethanes. Artif Org 13:144–147.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

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

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1989-8_18

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5820-6

  • Online ISBN: 978-1-4615-1989-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics