Advertisement

Cytotechnology

, Volume 50, Issue 1–3, pp 163–179 | Cite as

Present and Future Developments in Hepatic Tissue Engineering for Liver Support Systems

State of the art and future developments of hepatic cell culture techniques for the use in liver support systems
  • Sonja Diekmann
  • Augustinus Bader
  • Stephanie Schmitmeier
Article

Abstract

The liver is the most important organ for the biotransformation of xenobiotics, and the failure to treat acute or acute-on-chronic liver failure causes high mortality rates in affected patients. Due to the lack of donor livers and the limited possibility of the clinical management there has been growing interest in the development of extracorporeal liver support systems as a bridge to liver transplantation or to support recovery during hepatic failure. Earlier attempts to provide liver support comprised non-biological therapies based on the use of conventional detoxification procedures, such as filtration and dialysis. These techniques, however, failed to meet the expected efficacy in terms of the overall survival rate due to the inadequate support of several essential liver-specific functions. For this reason, several bioartificial liver support systems using isolated viable hepatocytes have been constructed to improve the outcome of treatment for patients with fulminant liver failure by delivering essential hepatic functions. However, controlled trials (phase I/II) with these systems have shown no significant survival benefits despite the systems’ contribution to improvements in clinical and biochemical parameters. For the development of improved liver support systems, critical issues, such as the cell source and culture conditions for the long-term maintenance of liver-specific functions in vitro, are reviewed in this article. We also discuss aspects concerning the performance, biotolerance and logistics of the selected bioartificial liver support systems that have been or are currently being preclinically and clinically evaluated.

Key words

Bioartificial liver Hepatocytes Liver failure Liver support systems 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Auth M.K., Okamoto M., Ishida Y., Keogh A., Auth S.H., Gerlach J., Encke A., McMaster P. and Strain A.J. (1998). Maintained function of primary human hepatocytes by cellular interactions in coculture: implications for liver support systems. Transpl. Int. 11: S439–S443Google Scholar
  2. Babensee J.E., De Boni U. and Sefton M.V. (1992). Morphological assessment of hepatoma cells (HepG2) microencapsulated in a HEMA-MMA copolymer with and without Matrigel. J. Biomed. Mater. Res. 26: 1401–1418CrossRefGoogle Scholar
  3. Bader A., Fruhauf N., Zech K., Haverich A. and Borlak J.T. (1998). Development of a small-scale bioreactor for drug metabolism studies maintaining hepatospecific functions. Xenobiotica 28: 815–825CrossRefGoogle Scholar
  4. Bader A., Knop E., Kern A., Boker K., Fruhauf N., Crome O., Esselmann H., Pape C., Kempka G. and Sewing K.F. (1996). 3-D coculture of hepatic sinusoidal cells with primary hepatocytes-design of an organotypical model. Exp. Cell Res. 226: 223–233CrossRefGoogle Scholar
  5. Bader A., Rinkes I.H., Closs E.I., Ryan C.M., Toner M., Cunningham J.M., Tompkins R.G. and Yarmush M.L. (1992). A stable long-term hepatocyte culture system for studies of physiologic processes: cytokine stimulation of the acute phase response in rat and human hepatocytes. Biotechnol. Prog. 8: 219–225CrossRefGoogle Scholar
  6. Baquerizo A., Mhoyan A., Kearns-Jonker M., Arnaout W.S., Shackleton C., Busuttil R.W., Demetriou A.A. and Cramer D.V. (1999). Characterization of human xenoreactive antibodies in liver failure patients exposed to pig hepatocytes after bioartificial liver treatment: an ex vivo model of pig to human xenotransplantation. Transplantation 67: 5–18CrossRefGoogle Scholar
  7. Ben-Ze’ev A., Robinson G.S., Bucher N.L. and Farmer S.R. (1988). Cell–cell and cell–matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of rat hepatocytes. Proc. Natl. Acad. Sci. U.S.A. 85: 2161–2165CrossRefGoogle Scholar
  8. Black D., Lyman S., Heider T.R. and Behrns K.E. (2004). Molecular and cellular features of hepatic regeneration. J. Surg. Res. 117: 306–315CrossRefGoogle Scholar
  9. Blusch J.H., Patience C. and Martin U. (2002). Pig endogenous retroviruses and xenotransplantation. Xenotransplantation 9: 242–251CrossRefGoogle Scholar
  10. Braet F., Shleper M., Paizi M., Brodsky S., Kopeiko N., Resnick N. and Spira G. (2004). Liver sinusoidal endothelial cell modulation upon resection and shear stress in vitro. Comp. Hepatol. 3: 7 CrossRefGoogle Scholar
  11. Bucher N.L., Robinson G.S. and Farmer S.R. (1990). Effects of extracellular matrix on hepatocyte growth and gene expression: implications for hepatic regeneration and the repair of liver injury. Semin. Liver Dis. 10: 11–19CrossRefGoogle Scholar
  12. Canaple L., Nurdin N., Angelova N., Hunkeler D. and Desvergne B. (2001). Development of a coculture model of encapsulated cells. Ann. NY Acad. Sci. 944: 350–361CrossRefGoogle Scholar
  13. Cascio S.M. (2001). Novel strategies for immortalization of human hepatocytes. Artif. Organs 25: 529–538CrossRefGoogle Scholar
  14. Costa R.H., Kalinichenko V.V., Holterman A.X. and Wang X. (2003). Transcription factors in liver development differentiation, and regeneration. Hepatology 38: 1331–1347Google Scholar
  15. Curcio E., Barbieri G., Rende M., Giorno L., Morelli S. and Drioli E. (2005). Diffusive and convective transport through hollow fiber membranes for liver cell culture. J. Biotechnol. 117: 309–321CrossRefGoogle Scholar
  16. David B., Dore E., Jaffrin M.Y. and Legallais C. (2004). Mass transfers in a fluidized bed bioreactor using alginate beads for a future bioartificial liver. Int. J. Artif. Organs 27: 284–293Google Scholar
  17. De Bartolo L., Bader A. (2001). Review of a flat membrane bioreactor as a bioartificial liver. Ann. Transplant. 6: 40–46Google Scholar
  18. De Bartolo L., Jarosch-Von Schweder G., Haverich A. and Bader A. (2000). A novel full-scale flat membrane bioreactor utilizing porcine hepatocytes: cell viability and tissue-specific functions. Biotechnol. Prog. 16: 102–108CrossRefGoogle Scholar
  19. De Bartolo L., Morelli S., Bader A. and Drioli E. (2002). Evaluation of cell behaviour related to physico-chemical properties of polymeric membranes to be used in bioartificial organs. Biomaterials 23: 2485–2497CrossRefGoogle Scholar
  20. De Bartolo L., Morelli S., Lopez L.C., Giorno L., Campana C., Salerno S., Rende M., Favia P., Detomaso L., Gristina R., d’Agostino R. and Drioli E. (2005). Biotransformation and liver-specific functions of human hepatocytes in culture on RGD-immobilized plasma-processed membranes. Biomaterials 26: 4432–4441CrossRefGoogle Scholar
  21. De Bartolo L., Morelli S., Rende M., Gordano A. and Drioli E. (2004). New modified polyetheretherketone membrane for liver cell culture in biohybrid systems: adhesion and specific functions of isolated hepatocytes. Biomaterials 25: 3621–3629CrossRefGoogle Scholar
  22. De Leeuw A.M., Brouwer A. and Knook D.L. (1990). Sinusoidal endothelial cells of the liver: fine structure and function in relation to age. J. Electron. Microsc. Tech. 14: 218–236CrossRefGoogle Scholar
  23. De Vos P., De Haan B. and Van Schilfgaarde R. (1997). Effect of the alginate composition on the biocompatibility of alginate-polylysine microcapsules. Biomaterials 18: 273–278CrossRefGoogle Scholar
  24. Demetriou A.A., Brown R.S., Busuttil R.W., Fair J., McGuire B.M., Rosenthal P., Am Esch J.S., Lerut J., Nyberg S.L., Salizzoni M., Fagan E.A., Broelsch C.E., Muraca M., Salmeron J.M., Rabkin J.M., Metselaar H.J., Pratt D., La Mata M., McChesney L.P., Everson G.T., Lavin P.T., Stevens A.C., Pitkin Z. and Solomon B.A. (2004). Prospectiverandomizedmulticentercontrolled trial of a bioartificial liver in treating acute liver failure. Ann. Surg. 239: 660–667CrossRefGoogle Scholar
  25. Dixit V., Darvasi R., Arthur M., Lewin K. and Gitnick G. (1993). Cryopreserved microencapsulated hepatocytes–transplantation studies in Gunn rats. Transplantation 55: 616–622CrossRefGoogle Scholar
  26. Dixit V. and Gitnick G. (1998). The bioartificial liver: state-of-the-art. Eur. J. Surg. 582(Suppl.): S71–S76Google Scholar
  27. Dore E. and Legallais C. (1999). A new concept of bioartificial liver based on a fluidized bed bioreactor. Ther. Apher. 3: 264–267CrossRefGoogle Scholar
  28. Dou M., de Sousa G., Lacarelle B., Placidi M., la Porte P., Domingo M., Lafont H. and Rahmani R. (1992). Thawed human hepatocytes in primary culture. Cryobiology 29: 454–469CrossRefGoogle Scholar
  29. Dunn J.C., Tompkins R.G. and Yarmush M.L. (1991). Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol. Prog. 7: 237–245CrossRefGoogle Scholar
  30. Dunn J.C., Tompkins R.G. and Yarmush M.L. (1992). Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation. J. Cell Biol. 116: 1043–1053CrossRefGoogle Scholar
  31. Dunn J.C., Yarmush M.L., Koebe H.G. and Tompkins R.G. (1989). Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. Faseb. J. 3: 174–177Google Scholar
  32. Ellis A.J., Hughes R.D., Wendon J.A., Dunne J., Langley P.G., Kelly J.H., Gislason G.T., Sussman N.L. and Williams R. (1996). Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology 24: 1446–1451CrossRefGoogle Scholar
  33. Elvevold K.H., Nedredal G.I., Revhaug A. and Smedsrod B. (2004). Scavenger properties of cultivated pig liver endothelial cells. Comp. Hepatol. 3: 4CrossRefGoogle Scholar
  34. Enomoto K., Nishikawa Y., Omori Y., Tokairin T., Yoshida M., Ohi N., Nishimura T., Yamamoto Y. and Li Q. (2004). Cell biology and pathology of liver sinusoidal endothelial cells. Med. Electron. Microsc. 37: 208–215CrossRefGoogle Scholar
  35. Eschbach E., Chatterjee S.S., Noldner M., Gottwald E., Dertinger H., Weibezahn K.F. and Knedlitschek G. (2005). Microstructured scaffolds for liver tissue cultures of high cell density: morphological and biochemical characterization of tissue aggregates. J. Cell Biochem. 95: 243–255CrossRefGoogle Scholar
  36. Evenepoel P., Laleman W., Wilmer A., Claes K., Maes B., Kuypers D., Bammens B., Nevens F. and Vanrenterghem Y. (2005). Detoxifying capacity and kinetics of prometheus — a new extracorporeal system for the treatment of liver failure. Blood Purif. 23: 349–358CrossRefGoogle Scholar
  37. Fishman J.A. and Patience C. (2004). Xenotransplantation: infectious risk revisited. Am. J. Transplant. 4: 1383–1390CrossRefGoogle Scholar
  38. Flendrig L.M., Calise F., Di Florio E., Mancini A., Ceriello A., Santaniello W., Mezza E., Sicoli F., Belleza G., Bracco A., Cozzolino S., Scala D., Mazzone M., Fattore M., Gonzales E. and Chamuleau R.A. (1999). Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver. Int. J. Artif. Organs 22: 701–709Google Scholar
  39. Flendrig L.M., la Soe J.W., Jorning G.G., Steenbeek A., Karlsen O.T., Bovee W.M., Ladiges N.C., te Velde A.A. and Chamuleau R.A. (1997). In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates. J. Hepatol. 26: 1379–1392CrossRefGoogle Scholar
  40. Fremond B., Malandain C., Guyomard C., Chesne C., Guillouzo A. and Campion J.P. (1993). Correction of bilirubin conjugation in the Gunn rat using hepatocytes immobilized in alginate gel beads as an extracorporeal bioartificial liver. Cell Transplant. 2: 453–460Google Scholar
  41. Fruhauf N.R., Oldhafer K.J., Holtje M., Kaiser G.M., Fruhauf J.H., Stavrou G.A., Bader A. and Broelsch C.E. (2004). A bioartificial liver support system using primary hepatocytes: a preclinical study in a new porcine hepatectomy model. Surgery 136: 47–56CrossRefGoogle Scholar
  42. Gan J.H., Zhou X.Q., Qin A.L., Luo E.P., Zhao W.F., Yu H. and Xu J. (2005). Hybrid artificial liver support system for treatment of severe liver failure. World J. Gastroenterol. 11: 890–894Google Scholar
  43. Gerlach J.C. (1996). Development of a hybrid liver support system: a review. Int. J. Artif. Organs 19: 645–654Google Scholar
  44. Gerlach J.C., Kloppel K., Muller C., Schnoy N., Smith M.D. and Neuhaus P. (1993). Hepatocyte aggregate culture technique for bioreactors in hybrid liver support systems. Int. J. Artif. Organs 16: 843–846Google Scholar
  45. Gerlach J.C., Mutig K., Sauer I.M., Schrade P., Efimova E., Mieder T., Naumann G., Grunwald A., Pless G., Mas A., Bachmann S., Neuhaus P. and Zeilinger K. (2003). Use of primary human liver cells originating from discarded grafts in a bioreactor for liver support therapy and the prospects of culturing adult liver stem cells in bioreactors: a morphologic study. Transplantation 76: 781–786CrossRefGoogle Scholar
  46. Gimson A.E. (1996). Fulminant and late onset hepatic failure. Br. J. Anaesth. 77: 90–98Google Scholar
  47. Glicklis R., Merchuk J.C. and Cohen S. (2004). Modeling mass transfer in hepatocyte spheroids via cell viability, spheroid sizeand hepatocellular functions. Biotechnol. Bioeng. 86: 672–680CrossRefGoogle Scholar
  48. Glicklis R., Shapiro L., Agbaria R., Merchuk J.C. and Cohen S. (2000). Hepatocyte behavior within three-dimensional porous alginate scaffolds. Biotechnol. Bioeng. 67: 344–353CrossRefGoogle Scholar
  49. Gregory P.G., Connolly C.K., Toner M. and Sullivan S.J. (2000). In vitro characterization of porcine hepatocyte function. Cell Transplant. 9: 1–10Google Scholar
  50. Guillouzo A., Rialland L., Fautrel A. and Guyomard C. (1999). Survival and function of isolated hepatocytes after cryopreservation. Chem. Biol. Interact. 121: 7–16CrossRefGoogle Scholar
  51. Hasegawa H., Shimada M., Gion T., Ijima H., Nakazawa K., Funatsu K. and Sugimachi K. (1999). Modulation of immunologic reactions between cultured porcine hepatocytes and human sera. ASAIO J. 45: 392–396CrossRefGoogle Scholar
  52. He Z.P., Tan W.Q., Tang Y.F. and Feng M.F. (2003). Differentiation of putative hepatic stem cells derived from adult rats into mature hepatocytes in the presence of epidermal growth factor and hepatocyte growth factor. Differentiation 71: 281–290CrossRefGoogle Scholar
  53. Hengstler J.G., Ringel M., Biefang K., Hammel S., Milbert U., Gerl M., Klebach M., Diener B., Platt K.L., Bottger T., Steinberg P. and Oesch F. (2000). Cultures with cryopreserved hepatocytes: applicability for studies of enzyme induction. Chem. Biol. Interact. 125: 51–73CrossRefGoogle Scholar
  54. Hoekstra R. and Chamuleau R.A. (2002). Recent developments on human cell lines for the bioartificial liver. Int. J. Artif. Organs 25: 182–191Google Scholar
  55. Honiger J., Sarkis R., Baudrimont M., Delelo R., Chafai N., Benoist S., Sarkis K., Balladur P., Capeau J. and Nordlinger B. (2000). Semiautomatic macroencapsulation of large numbers of porcine hepatocytes by coextrusion with a solution of AN69 polymer. Biomaterials 21: 1269–1274CrossRefGoogle Scholar
  56. Hughes R.D., Nicolaou N., Langley P.G., Ellis A.J., Wendon J.A. and Williams R. (1998). Plasma cytokine levels and coagulation and complement activation during use of the extracorporeal liver assist device in acute liver failure. Artif. Organs 22: 854–858CrossRefGoogle Scholar
  57. Irgang M., Sauer I.M., Karlas A., Zeilinger K., Gerlach J.C., Kurth R., Neuhaus P. and Denner J. (2003). Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. J. Clin. Virol. 28: 141–154CrossRefGoogle Scholar
  58. Isom H.C., Secott T., Georgoff I., Woodworth C. and Mummaw J. (1985). Maintenance of differentiated rat hepatocytes in primary culture. Proc. Natl. Acad. Sci. U.S.A. 82: 3252–3256CrossRefGoogle Scholar
  59. Jasmund I., Langsch A., Simmoteit R. and Bader A. (2002). Cultivation of primary porcine hepatocytes in an OXY-HFB for use as a bioartificial liver device. Biotechnol. Prog. 18: 839–846CrossRefGoogle Scholar
  60. Jauregui H.O., Mullon C.J., Trenkler D., Naik S., Santangini H., Press P., Muller T.E. and Solomon B.A. (1995). In vivo evaluation of a hollow fiber liver assist device. Hepatology 21: 460–469CrossRefGoogle Scholar
  61. Jauregui H.O., Naik S., Santangini H., Pan J., Trenkler D. and Mullon C. (1994). Primary cultures of rat hepatocytes in hollow fiber chambers. In Vitro Cell Dev Biol. Anim. 30: 23–29CrossRefGoogle Scholar
  62. Joly A., Desjardins J.F., Fremond B., Desille M., Campion J.P., Malledant Y., Lebreton Y., Semana G., Edwards-Levy F., Levy M.C. and Clement B. (1997). Survival, proliferation, and functions of porcine hepatocytes encapsulated in coated alginate beads: a step toward a reliable bioartificial liver. Transplantation 63: 795–803CrossRefGoogle Scholar
  63. Kang Y.H., Berthiaume F., Nath B.D. and Yarmush M.L. (2004). Growth factors and nonparenchymal cell conditioned media induce mitogenic responses in stable long-term adult rat hepatocyte cultures. Exp. Cell Res. 293: 239–247CrossRefGoogle Scholar
  64. King A., Strand B., Rokstad A.M., Kulseng B., Andersson A., Skjak-Braek G. and Sandler S. (2003). Improvement of the biocompatibility of alginate/poly-l-lysine/alginate microcapsules by the use of epimerized alginate as a coating. J. Biomed. Mater. Res. (Part) A. 64: 533–539CrossRefGoogle Scholar
  65. Kjaergard L.L., Liu J., Als-Nielsen B. and Gluud C. (2003). Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA 289: 217–222CrossRefGoogle Scholar
  66. Kmieć Z. (2001). Cooperation of liver cells in health and disease. In: Beck, F., Christ, B., Kriz, W., Kummer, W., Marani, E., Putz, R., Sano, Y., Schiebler, T.H., Schoenwolf, G.C. and Zilles, K. (eds) Advances in Anatomy Embryology and Cell Biology, Vol. 161, pp 1–149. Springer-Verlag, Berlin, Heidelberg, New YorkGoogle Scholar
  67. Kobayashi N., Okitsu T., Nakaji S. and Tanaka N. (2003). Hybrid bioartificial liver: establishing a reversibly immortalized human hepatocyte line and developing a bioartificial liver for practical use. J. Artif. Organs 6: 236–244CrossRefGoogle Scholar
  68. Koide N., Sakaguchi K., Koide Y., Asano K., Kawaguchi M., Matsushima H., Takenami T., Shinji T., Mori M. and Tsuji T. (1990). Formation of multicellular spheroids composed of adult rat hepatocytes in dishes with positively charged surfaces and under other nonadherent environments. Exp. Cell Res. 186: 227–235CrossRefGoogle Scholar
  69. Koniaris L.G., McKillop I.H., Schwartz S.I. and Zimmers T.A. (2003). Liver regeneration. J. Am. Coll. Surg. 197: 634–659CrossRefGoogle Scholar
  70. Krisper P., Haditsch B., Stauber R., Jung A., Stadlbauer V., Trauner M., Holzer H. and Schneditz D. (2005). In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation. J. Hepatol. 43: 451–457CrossRefGoogle Scholar
  71. Kuddus R., Patzer J.F., Lopez R., Mazariegos G.V., Meighen B., Kramer D.J. and Rao A.S. (2002). Clinical and laboratory evaluation of the safety of a bioartificial liver assist device for potential transmission of porcine endogenous retrovirus. Transplantation 73: 420–429CrossRefGoogle Scholar
  72. Lacik I., Brissova M., Anilkumar A.V., Powers A.C. and Wang T. (1998). New capsule with tailored properties for the encapsulation of living cells. J. Biomed. Mater. Res. 39: 52–60CrossRefGoogle Scholar
  73. Langsch A. and Bader A. (2001). Longterm stability of phase I and phase II enzymes of porcine liver cells in flat membrane bioreactors. Biotechnol. Bioeng. 76: 115–125CrossRefGoogle Scholar
  74. Lee K.W., Park J.B., Yoon J.J., Lee J.H., Kim S.Y., Jung H.J., Lee S.K., Kim S.J., Lee H.H., Lee D.S. and Joh J.W. (2004). The viability and function of cryopreserved hepatocyte spheroids with different cryopreservation solutions. Transplant. Proc. 36: 2462–2463CrossRefGoogle Scholar
  75. Lee W.M. (1993). Acute liver failure. N. Engl. J. Med. 329: 1862–1872CrossRefGoogle Scholar
  76. Legallais C., Dore E. and Paullier P. (2000). Design of a fluidized bed bioartificial liver. Artif. Organs 24: 519–525CrossRefGoogle Scholar
  77. Lorenti A., Barbich M., de Santibanes M., Ielpi M., Vazquez J.C., Sorroche P. and Argibay P. (2003). Ammonium detoxification performed by porcine hepatocyte spheroids in a bioartificial liver for pediatric use: preliminary report. Artif. Organs 27: 665–670CrossRefGoogle Scholar
  78. Louha M., Poussin K., Ganne N., Zylberberg H., Nalpas B., Nicolet J., Capron F., Soubrane O., Vons C., Pol S., Beaugrand M, Berthelot P., Franco D., Trinchet J.C., Brechot C. and Paterlini P. (1997). Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer. Hepatology 26: 998–1005CrossRefGoogle Scholar
  79. Lowes K.N., Croager E.J., Olynyk J.K., Abraham L.J. and Yeoh G.C. (2003). Oval cell-mediated liver regeneration: Role of cytokines and growth factors. J. Gastroenterol. Hepatol. 18: 4–12CrossRefGoogle Scholar
  80. Mai G., Huy N.T., Morel P., Mei J., Bosco D., Berney T., Majno P., Mentha G., Trono D. and Buhler L.H. (2005). Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes. Transplant. Proc. 37: 527–529CrossRefGoogle Scholar
  81. Martinez-Hernandez A. and Amenta P.S. (1993). The hepatic extracellular matrix. I. Components and distribution in normal liver. Virchows Arch. A. Pathol. Anat. Histopathol. 423: 1–11CrossRefGoogle Scholar
  82. Matsushita T., Yagi T., Hardin J.A., Cragun J.D., Crow F.W., Bergen H.R., Gores G.J. and Nyberg S.L. (2003). Apoptotic cell death and function of cryopreserved porcine hepatocytes in a bioartificial liver. Cell Transplant. 12: 109–121Google Scholar
  83. Mazariegos G.V., Kramer D.J., Lopez R.C., Shakil A.O., Rosenbloom A.J., DeVera M., Giraldo M., Grogan T.A., Zhu Y., Fulmer M.L., Amiot B.P. and Patzer J.F. (2001). Safety observations in phase I clinical evaluation of the Excorp Medical Bioartificial Liver Support System after the first four patients. ASAIO J. 47: 471–475CrossRefGoogle Scholar
  84. McClelland R.E., MacDonald J.M. and Coger R.N. (2003). Modeling O2 transport within engineered hepatic devices. Biotechnol. Bioeng. 82: 12–27CrossRefGoogle Scholar
  85. McLaughlin B.E., Tosone C.M., Custer L.M. and Mullon C. (1999). Overview of extracorporeal liver support systems and clinical results. Ann. NY Acad. Sci. 875: 310–325CrossRefGoogle Scholar
  86. Michalopoulos G.K., Bowen W.C., Mule K. and Stolz D.B. (2001). Histological organization in hepatocyte organoid cultures. Am. J. Pathol. 159: 1877–1887Google Scholar
  87. Michalopoulos G.K. and DeFrances M.C. (1997). Liver regeneration. Science 276: 60–66CrossRefGoogle Scholar
  88. Mitzner S.R., Stange J., Klammt S., Peszynski P. and Schmidt R. (2001). Albumin dialysis using the molecular adsorbent recirculating system. Curr. Opin. Nephrol. Hypertens. 10: 777–783CrossRefGoogle Scholar
  89. Miura Y., Akimoto T. and Yagi K. (1988). Liver functions in hepatocytes entrapped within calcium alginate. Ann. NY Acad. Sci. 542: 521–532CrossRefGoogle Scholar
  90. Morsiani E., Brogli M., Galavotti D., Bellini T., Ricci D., Pazzi P. and Puviani A.C. (2001). Long-term expression of highly differentiated functions by isolated porcine hepatocytes perfused in a radial–flow bioreactor. Artif. Organs 25: 740–748CrossRefGoogle Scholar
  91. Morsiani E., Brogli M., Galavotti D., Pazzi P., Puviani A.C. and Azzena G.F. (2002a). Biologic liver support: optimal cell source and mass. Int. J. Artif. Organs 25: 985–993Google Scholar
  92. Morsiani E., Pazzi P., Puviani A.C., Brogli M., Valieri L., Gorini P., Scoletta P., Marangoni E., Ragazzi R., Azzena G., Frazzoli E., Di Luca D. and Cassai E. (2002b). Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients. Int. J. Artif. Organs 25: 192–202Google Scholar
  93. Muraca M., Vilei M.T., Zanusso E., Ferraresso C., Granato A., Doninsegna S., Dal Monte R., Carraro P. and Carturan G. (2000). Encapsulation of hepatocytes by SiO(2). Transplant Proc. 32: 2713–2714CrossRefGoogle Scholar
  94. Muto Y., Nouri-Aria K.T., Meager A., Alexander G.J., Eddleston A.L. and Williams R. (1988). Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. Lancet 2: 72–74CrossRefGoogle Scholar
  95. Nagy A. (2000). Cre recombinase: the universal reagent for genome tailoring. Genesis 26: 99–109CrossRefGoogle Scholar
  96. Nyberg S.L., Hibbs J.R., Hardin J.A., Germer J.J. and Persing D.H. (1999). Transfer of porcine endogenous retrovirus across hollow fiber membranes: significance to a bioartificial liver. Transplantation 67: 1251–1255CrossRefGoogle Scholar
  97. Nyberg S.L., Mann H.J., Hu M.Y., Payne W.D., Hu W.S., Cerra F.B. and Remmel R.P. (1996). Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit. Drug Metab. Dispos. 24: 643–648Google Scholar
  98. Nyberg S.L., Platt J.L., Shirabe K., Payne W.D., Hu W.S. and Cerra F.B. (1992a). Immunoprotection of xenocytes in a hollow fiber bioartificial liver. ASAIO J. 38: M463–M467CrossRefGoogle Scholar
  99. Nyberg S.L., Shatford R.A., Hu W.S., Payne W.D. and Cerra F.B. (1992b). Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support). Crit. Care Med. 20: 1157–1168CrossRefGoogle Scholar
  100. Nyberg S.L., Shatford R.A., Payne W.D., Hu W.S. and Cerra F.B. (1992c). Primary culture of rat hepatocytes entrapped in cylindrical collagen gels: an in vitro system with application to the bioartificial liver. Rat hepatocytes cultured in cylindrical collagen gels. Cytotechnology 10: 205–215CrossRefGoogle Scholar
  101. Nyberg S.L., Shirabe K., Peshwa M.V., Sielaff T.D., Crotty P.L., Mann H.J., Remmel R.P., Payne W.D., Hu W.S. and Cerra F.B. (1993). Extracorporeal application of a gel-entrapmentbioartificial liver: demonstration of drug metabolism and other biochemical functions. Cell Transplant. 2: 441–452Google Scholar
  102. Orive G., Hernandez R.M., Gascon A.R., Calafiore R., Chang T.M., De Vos P., Hortelano G., Hunkeler D., Lacik I., Shapiro A.M. and Pedraz J.L. (2003). Cell encapsulation: promise and progress. Nat. Med. 9: 104–107CrossRefGoogle Scholar
  103. Orive G., Hernandez R.M., Rodriguez Gascon A., Calafiore R., Chang T.M., de Vos P., Hortelano G., Hunkeler D., Lacik I. and Pedraz J.L (2004). History, challenges and perspectives of cell microencapsulation. Trends Biotechnol. 22: 87–92CrossRefGoogle Scholar
  104. Pahernik S.A., Thasler W.E., Doser M., Gomez-Lechon M.J., Castell M.J., Planck H. and Koebe H.G. (2001). High density culturing of porcine hepatocytes immobilized on nonwoven polyurethane-based biomatrices. Cells Tissues Organs 168: 170–177CrossRefGoogle Scholar
  105. Pitkin Z. and Mullon C. (1999). Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system. Artif. Organs 23: 829–833CrossRefGoogle Scholar
  106. Quek C.H., Li J., Sun T., Chan M.L., Mao H.Q., Gan L.M., Leong K.W. and Yu H. (2004). Photo-crosslinkable microcapsules formed by polyelectrolyte copolymer and modified collagen for rat hepatocyte encapsulation. Biomaterials 25: 3531–3540CrossRefGoogle Scholar
  107. Rahman T. and Hodgson H. (2001). Clinical management of acute hepatic failure. Intensive Care Med. 27: 467–476CrossRefGoogle Scholar
  108. Ramadori G. and Armbrust T. (2001). Cytokines in the liver. Eur. J. Gastroenterol. Hepatol. 13: 777–784CrossRefGoogle Scholar
  109. Rifai K., Bahr M., Schneider A., Ott M. and Mann M. (2003). Neue Verfahren in der Leberersatztherapie. Medizinische Klinik 98: 750–753CrossRefGoogle Scholar
  110. Runge D., Runge D.M., Jager D., Lubecki K.A., Beer Stolz D., Karathanasis S., Kietzmann T., Strom S.C., Jungermann K., Fleig W.E. and Michalopoulos G.K. (2000). Serum-freelong-term cultures of human hepatocytes: maintenance of cell morphology, transcription factors, and liver-specific functions. Biochem. Biophys. Res. Commun. 269: 46–53CrossRefGoogle Scholar
  111. Saad B., Scholl F.A., Thomas H., Schawalder H., Streit V., Waechter F. and Maier P. (1993). Crude liver membrane fractions and extracellular matrix components as substrata regulate differentially the preservation and inducibility of cytochrome P-450 isoenzymes in cultured rat hepatocytes. Eur. J. Biochem. 213: 805–814CrossRefGoogle Scholar
  112. Sakai Y., Naruse K., Nagashima I., Muto T. and Suzuki M. (1996). Large-scale preparation and function of porcine hepatocyte spheroids. Int. J. Artif. Organs 19: 294–301Google Scholar
  113. Sato Y., Tsukada K. and Hatakeyama K. (1999). Role of shear stress and immune responses in liver regeneration after a partial hepatectomy. Surg. Today 29: 1–9CrossRefGoogle Scholar
  114. Sauer I.M. and Gerlach J.C. (2002). Modular extracorporeal liver support. Artif. Organs 26: 703–706CrossRefGoogle Scholar
  115. Sauer I.M., Kardassis D., Zeillinger K., Pascher A., Gruenwald A., Pless G., Irgang M., Kraemer M., Puhl G., Frank J., Muller A.R., Steinmuller T., Denner J., Neuhaus P. and Gerlach J.C. (2003). Clinical extracorporeal hybrid liver support–phase I study with primary porcine liver cells. Xenotransplantation 10: 460–469CrossRefGoogle Scholar
  116. Sauer I.M., Obermeyer N., Kardassis D., Theruvath T. and Gerlach J.C. (2001). Development of a hybrid liver support system. Ann. NY Acad. Sci. 944: 308–319CrossRefGoogle Scholar
  117. Sauer I.M., Zeilinger K., Obermayer N., Pless G., Grunwald A., Pascher A., Mieder T., Roth S., Goetz M., Kardassis D., Mas A., Neuhaus P. and Gerlach J.C. (2002). Primary human liver cells as source for modular extracorporeal liver support–a preliminary report. Int. J. Artif. Organs 25: 1001–1005Google Scholar
  118. Schoen J.M., Wang H.H., Minuk G.Y. and Lautt W.W. (2001). Shear stress-induced nitric oxide release triggers the liver regeneration cascade. Nitric Oxide 5: 453–464CrossRefGoogle Scholar
  119. Schuetz E.G., Li D., Omiecinski C.J., Muller-Eberhard U., Kleinman H.K., Elswick B. and Guzelian P.S. (1988). Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. J. Cell Physiol. 134: 309–323CrossRefGoogle Scholar
  120. Semino C.E., Merok J.R., Crane G.G., Panagiotakos G. and Zhang S. (2003). Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds. Differentiation 71: 262–270CrossRefGoogle Scholar
  121. Seo S.J., Akaike T., Choi Y.J., Shirakawa M., Kang I.K. and Cho C.S. (2005). Alginate microcapsules prepared with xyloglucan as a synthetic extracellular matrix for hepatocyte attachment. Biomaterials 26: 3607–3615CrossRefGoogle Scholar
  122. Serandour A.L., Loyer P., Garnier D., Courselaud B., Theret N., Glaise D., Guguen-Guillouzo C. and Corlu A. (2005). TNFα-mediated extracellular matrix remodeling is required for multiple division cycles in rat hepatocytes. Hepatology 41: 478–486CrossRefGoogle Scholar
  123. Shito M., Tilles A.W., Tompkins R.G., Yarmush M.L. and Toner M. (2003). Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure. J. Surg. Res. 111: 53–62CrossRefGoogle Scholar
  124. Sielaff T.D., Hu M.Y., Rao S., Groehler K., Olson D., Mann H.J., Remmel R.P., Shatford R.A., Amiot B. and Hu W.S. (1995). A technique for porcine hepatocyte harvest and description of differentiated metabolic functions in static culture. Transplantation 59: 1459–1463CrossRefGoogle Scholar
  125. Stange J. and Mitzner S. (1996). Hepatocyte encapsulation–initial intentions and new aspects for its use in bioartificial liver support. Int. J. Artif. Organs 19: 45–48Google Scholar
  126. Sussman N.L., Chong M.G., Koussayer T., He D.E., Shang T.A., Whisennand H.H. and Kelly J.H. (1992). Reversal of fulminant hepatic failure using an extracorporeal liver assist device. Hepatology 16: 60–65CrossRefGoogle Scholar
  127. Sussman N.L. and Kelly J.H. (1993). Improved liver function following treatment with an extracorporeal liver assist device. Artif. Organs 17: 27–30CrossRefGoogle Scholar
  128. Suzuki A., Iwama A., Miyashita H., Nakauchi H. and Taniguchi H. (2003). Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development 130: 2513–2524CrossRefGoogle Scholar
  129. Taub R. (2004). Liver regeneration: from myth to mechanism. Nat. Rev. Mol. Cell Biol. 5: 836–847CrossRefGoogle Scholar
  130. te Velde A.A., Ladiges N.C., Flendrig L.M. and Chamuleau R.A. (1995). Functional activity of isolated pig hepatocytes attached to different extracellular matrix substrates. Implication for application of pig hepatocytes in a bioartificial liver. J. Hepatol. 23: 184–192Google Scholar
  131. Tong J.Z., Sarrazin S., Cassio D., Gauthier F. and Alvarez F. (1994). Application of spheroid culture to human hepatocytes and maintenance of their differentiation. Biol. Cell 81: 77–81CrossRefGoogle Scholar
  132. Tsiaoussis J., Newsome P.N., Nelson L.J., Hayes P.C. and Plevris J.N. (2001). Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems. Liver Transpl. 7: 2–10CrossRefGoogle Scholar
  133. Uludag H., De Vos P. and Tresco P.A. (2000). Technology of mammalian cell encapsulation. Adv. Drug Deliv. Rev. 42: 29–64CrossRefGoogle Scholar
  134. van de Kerkhove M.P., Germans M.R., Deurholt T., Hoekstra R., Joziasse D.H., van Wijk A.C., van Gulik T.M., Chamuleau R.A. and Roos A. (2005a). Evidence for Galα (1–3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems. J. Hepatol. 42: 541–547CrossRefGoogle Scholar
  135. van de Kerkhove M.P., Hoekstra R., Chamuleau R.A. and van Gulik T.M. (2004). Clinical application of bioartificial liver support systems. Ann. Surg. 240: 216–230CrossRefGoogle Scholar
  136. van de Kerkhove M.P. and Poyck P.P. (2005b). Liver support therapy: an overview of the AMC-bioartificial liver research. Dig. Surg. 22: 254–264CrossRefGoogle Scholar
  137. (1999). Cell-cell organization and functions of ‘sinusoids’ in liver microcirculation system. J. Electron. Microsc. (Tokyo) 48: 89–98Google Scholar
  138. (1999). Cultivation and characterization of a new immortalized human hepatocyte cell lineHepZ, for use in an artificial liver support system. Ann. NY Acad. Sci. 875: 364–368CrossRefGoogle Scholar
  139. (2003). Comparison of primary human hepatocytes and hepatoma cell line HepG2 with regard to their biotransformation properties. Drug Metab. Dispos. 31: 1035–1042CrossRefGoogle Scholar
  140. (2003). Biochemical and functional changes of rat liver spheroids during spheroid formation and maintenance in culture: II. nitric oxide synthesis and related changes. J. Cell Biochem. 90: 1176–1185CrossRefGoogle Scholar
  141. (2001). Self-organization of liver constitutive cells mediated by artificial matrix and improvement of liver functions in long-term culture. Biochem. Eng. J. 8: 135–143CrossRefGoogle Scholar
  142. (2003). Efficacy of a larger version of the hybrid artificial liver support system using a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure pig model for preclinical experiments. Cell Transplant. 12: 101–107 Google Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Sonja Diekmann
    • 1
  • Augustinus Bader
    • 1
  • Stephanie Schmitmeier
    • 1
  1. 1.Center for Biotechnology and Biomedicine, Cell Techniques and Applied Stem Cell BiotechnologyUniversity of LeipzigLeipzigGermany

Personalised recommendations