Stand der Hepatozytentransplantation: Risiko oder Chance?

'Abstract Over the past few years, hepatocyte transplantation has been considered as an alternative method for orthotopic liver transplantation for the treatment of various liver diseases. Beside curative approach for genetic metabolic deficiences (familial hypercholesterolemia, hemophilia, etc.), it could be a useful tool for bridging the waiting period until an appropriate donor organ is obtained. In preclinical animal studies, hepatocytes injected intraperitoneally, intraportally or into the spleen settle down in the diseased liver. This enables genetic modification to correct inborn metabolic deficiences and improves survival in acute liver failure. In 1992, the first clinical transplantation of isolated hepatocytes in 10 patients was performed. In 1998, Fox and coworkers described the succesful transplantation of allogeneic liver cells in a child with Crigler-Najjar syndrome. Accomplished studies of Strom et al. resp. Bilir et al. of the same year proved the effectiveness of liver cell transplantation for transient treatment of acute liver failure. Prerequisite of this cell-based therapeutic strategy is a sufficient amount of highly differentiated hepatocytes, hence, a well established in-vitro cell-culture technique is necessary to yield a reproducible number of proliferating hepatocytes and to preserve the physiological cell function. This review discusses the different experimental approaches regarding the cultivation of human hepatocytes and also the use of alternative cell sources (like animal hepatocytes, immortalized cells of human origin, progenitor cells from fetal human liver/liver stem cells) for hepatocyte transplantation.

[1]  E. Keeffe,et al.  Liver transplantation: current status and novel approaches to liver replacement. , 2001, Gastroenterology.

[2]  H. Malhi,et al.  Hepatocyte transplantation: new horizons and challenges. , 2001, Journal of hepato-biliary-pancreatic surgery.

[3]  B. Vikram,et al.  Liver irradiation: a potential preparative regimen for hepatocyte transplantation. , 2001, International journal of radiation oncology, biology, physics.

[4]  C. Hodgkinson,et al.  Fibronectin-mediated hepatocyte shape change reprograms cytochrome P450 2C11 gene expression via an integrin-signaled induction of ribonuclease activity. , 2000, Molecular pharmacology.

[5]  Xin Wang,et al.  Purified hematopoietic stem cells can differentiate into hepatocytes in vivo , 2000, Nature Medicine.

[6]  P. Maganto,et al.  Liver gene expression and increase in albumin synthesis by fetal hepatocytes transplanted into analbuminemic rats. , 2000, Life sciences.

[7]  E. Christensen,et al.  Effect on outcome of the lengthening waiting list for liver transplantation , 2000, Gut.

[8]  J. Furui,et al.  Intraportal administration of low-dose recombinant human hepatocyte growth factor enhances effects of hepatocellular transplantation. , 2000, Hepato-gastroenterology.

[9]  M. Manns,et al.  Emerging Therapies in Hepatology: Liver-Directed Gene Transfer and Hepatocyte Transplantation , 2000, Cells Tissues Organs.

[10]  A. Kahn,et al.  Therapeutic liver repopulation in a mouse model of hypercholesterolemia. , 2000, Human molecular genetics.

[11]  C. Palestro,et al.  Transplanted hepatocytes engraft, survive, and proliferate in the liver of rats with carbon tetrachloride‐induced cirrhosis , 2000, The Journal of pathology.

[12]  R. DePinho,et al.  Hepatocyte transplantation improves survival in mice with liver toxicity induced by hepatic overexpression of Mad1 transcription factor. , 2000, Molecular therapy : the journal of the American Society of Gene Therapy.

[13]  Y. Kwak,et al.  Systematic analysis of the effects of hepatocyte transplantation on rats with acute liver failure. , 2000, Hepato-gastroenterology.

[14]  J. Golmard,et al.  Analysis of the French liver transplant waiting list, 1992-1996. , 2000, Transplantation.

[15]  F M Watt,et al.  Out of Eden: stem cells and their niches. , 2000, Science.

[16]  E. Benedetti,et al.  Multiple intrasplenic hepatocyte transplantations in the dalmatian dog. , 2000, Surgery.

[17]  J. Vacanti,et al.  Alternatives to liver transplantation: from hepatocyte transplantation to tissue-engineered organs. , 2000, Gastroenterology.

[18]  Sunil Badve,et al.  Derivation of hepatocytes from bone marrow cells in mice after radiation‐induced myeloablation , 2000, Hepatology.

[19]  M. Toner,et al.  In Vitro Characterization of Porcine Hepatocyte Function , 2000, Cell transplantation.

[20]  D. Gottlieb,et al.  An in vitro Pathway from Embryonic Stem Cells to Neurons and Glia , 1999, Cells Tissues Organs.

[21]  N. Hole Embryonic Stem Cell-Derived Haematopoiesis , 1999, Cells Tissues Organs.

[22]  B. Fleischmann,et al.  Establishment of Ionic Channels and Signalling Cascades in the Embryonic Stem Cell-Derived Primitive Endoderm and Cardiovascular System , 1999, Cells Tissues Organs.

[23]  J. Gerlach,et al.  Treatment of acute liver failure: hybrid liver support , 1999, Langenbeck's Archives of Surgery.

[24]  M. Grompe Therapeutic liver repopulation for the treatment of metabolic liver diseases. , 1999, Human cell.

[25]  R Williams,et al.  Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis , 1999, Journal of gastroenterology and hepatology.

[26]  S. Yoshida,et al.  Up-regulation of telomerase in primary cultured rat hepatocytes. , 1999, Journal of biochemistry.

[27]  W. Mars,et al.  Bone marrow as a potential source of hepatic oval cells. , 1999, Science.

[28]  R. Fisher,et al.  Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion. , 1999, Transplantation.

[29]  M. Nozawa,et al.  Prolonged Function of Hepatocytes Transplanted into the Spleens of Nagase Analbuminemic Rats , 1999, European Surgical Research.

[30]  E. Laconi,et al.  Restoration of serum albumin levels in nagase analbuminemic rats by hepatocyte transplantation , 1999, Hepatology.

[31]  A. Demetriou,et al.  Artificial liver: review and Cedars-Sinai experience. , 1998, Journal of hepato-biliary-pancreatic surgery.

[32]  B. Tassinari,et al.  An update on high-yield hepatocyte isolation methods and on the potential clinical use of isolated liver cells. , 1998, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[33]  S. Strom,et al.  Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. , 1998, The New England journal of medicine.

[34]  R. Weiss,et al.  Two sets of human-tropic pig retrovirus , 1997, Nature.

[35]  N. Chowdhury,et al.  Treatment of surgically induced acute liver failure by transplantation of conditionally immortalized hepatocytes. , 1997, Transplantation.

[36]  E. Roberts,et al.  Extended primary culture of human hepatocytes in a collagen gel sandwich system , 1997, In Vitro Cellular & Developmental Biology - Animal.

[37]  Yasuhiro Takeuchi,et al.  Infection of human cells by an endogenous retrovirus of pigs , 1997, Nature Medicine.

[38]  R. Fisher,et al.  Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. , 1997, Transplantation.

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

[40]  A. Demetriou,et al.  Treatment of hypercholesterolemia in the Watanabe rabbit using allogeneic hepatocellular transplantation under a regeneration stimulus. , 1996, Transplantation.

[41]  I. B. Borel Rinkes,et al.  Correction of an inborn error of metabolism by intraportal hepatocyte transplantation in a dog model. , 1996, Transplantation.

[42]  M. Charron,et al.  The use of cultured hepatocyte infusion via the portal vein for the treatment of ornithine transcarbamoylase deficiency by transplantation of enzymatically competent ABO/Rh-matched cell , 1996 .

[43]  B. Markus,et al.  Effects of proinflammatory cytokines on cultivated primary human hepatocytes. Fluorometric measurement of intercellular adhesion molecule-1 and human leukocyte antigen-A, -B, -C, and -DR expression. , 1995, Transplantation.

[44]  M V Peshwa,et al.  Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver. , 1994, Annals of surgery.

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

[46]  M. Becich,et al.  Comparative analysis of mitogenic and morphogenic effects of HGF and EGF on rat and human hepatocytes maintained in collagen gels , 1993, Journal of cellular physiology.

[47]  M. Yarmush,et al.  Proline‐mediated enhancement of hepatocyte function in a collagen gel sandwich culture configuration , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[48]  M. Kusano,et al.  Hepatocyte Transplantation in Man , 1992, Transplantation proceedings.

[49]  O. Hino,et al.  Hepatocarcinogenesis in Transgenic Mice Carrying Albumin‐promoted SV40 T Antigen Gene , 1991, Japanese journal of cancer research : Gann.

[50]  G. Kondos,et al.  HEPATOCYTE TRANSPLANTATION FOR THE LOW‐DENSITY LIPOPROTEIN RECEPTOR‐DEFICIENT STATEA: A STUDY IN THE WATANABK RABBIT , 1990, Transplantation.

[51]  A. Matas,et al.  Hepatocellular transplantation in acute liver failure. , 1977, Surgery.

[52]  S. Strom,et al.  Hepatocyte transplantation for the treatment of human disease. , 1999, Seminars in liver disease.

[53]  H. Jauregui,et al.  Isolation and culture of porcine hepatocytes for artificial liver support. , 1996, Cell transplantation.

[54]  B. Markus,et al.  [Isolation and separation of human adult hepatocytes from resected liver: cellular yield and purity using different methods]. , 1994, Zentralblatt fur Chirurgie.

[55]  M. Rissel,et al.  Effect of hydrocortisone on deposition of types I and IV collagen in primary culture of rat hepatocytes. , 1988, Cellular and molecular biology.

[56]  L. C. Stevens Testicular, ovarian, and embryo-derived teratomas. , 1983 .