Semipermeable hollow fiber membranes in hepatocyte bioreactors: a prerequisite for a successful bioartificial liver?

Recent studies have shown that liver support systems based on viable hepatocytes can prolong life in animal models of acute liver failure. Now the time has come to elucidate the design characteristics that are essential to construct an efficient bioreactor. The gold standard remains the intact liver. Despite the very high cell density in this organ, individual cell perfusion is guaranteed resulting in low diffusional gradients which are essential for optimal mass transfer. These conditions are not met in bioreactors based on hollow fiber membranes. Moreover, the semipermeable membranes can foul and act as a diffusional barrier between the hepatocytes and the blood or plasma of the recipient. We devised a novel bioreactor for use as a bioartificial liver that does not include hollow fiber membranes for blood or plasma perfusion. The device is based on an integral oxygenator and a nonwoven polyester matrix material for hepatocyte culture as small aggregates. The efficacy of this original design was tested in rats with liver ischemia. Preliminary results show statistically significantly improved survival; life was prolonged 100% compared to the control experiments.

[1]  B. Fisher,et al.  Portacaval shunt in the rat. , 1961, Surgery.

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

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

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

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

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

[7]  C. Mullon,et al.  In vivo evaluation of a hollow fiber liver assist device , 1995, Hepatology.

[8]  L. Flendrig,et al.  Functional activity of isolated pig hepatocytes attached to different extracellular matrix substrates. Implication for application of pig hepatocytes in a bioartificial liver. , 1995, Journal of hepatology.

[9]  T. Akaike,et al.  High cell-density culture system of hepatocytes entrapped in a three-dimensional hollow fiber module with collagen gel. , 1995, Artificial organs.

[10]  F. Cerra,et al.  Gel-entrapment bioartificial liver therapy in galactosamine hepatitis. , 1995, The Journal of surgical research.

[11]  K. Oldhafer,et al.  A novel bioreactor design for in vitro reconstruction of in vivo liver characteristics. , 1995, Artificial organs.

[12]  P. C. Chau,et al.  Protein‐free human–human hybridoma cultures in an intercalated‐spiral alternate‐dead‐ended hollow fiber bioreactor , 1995, Biotechnology and bioengineering.

[13]  G Catapano,et al.  Mass Transfer Limitations to the Performance of Membrane Bioartificial Liver Support Devices , 1996, The International journal of artificial organs.

[14]  A. Demetriou,et al.  Clinical Experience with a Porcine Hepatocyte-Based Liver Support System , 1996, The International journal of artificial organs.

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

[16]  L. Flendrig,et al.  Immunological Consequences of the use of Xenogeneic Hepatocytes in a Bioartificial Liver for Acute Liver Failure , 1997, The International journal of artificial organs.

[17]  R. Busuttil,et al.  Xenoantibody response of patients with severe acute liver failure exposed to porcine antigens following treatment with a bioartificial liver. , 1997, Transplantation proceedings.

[18]  O. Karlsen,et al.  UvA-DARE ( Digital Academic Repository ) 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 , 2001 .