Article information
Abstract
Liver transplantation has been remarkably effective in the treatment in patients with endstage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation. Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients.
The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation.
In the Hospital La Fe of Valencia, we performed the first hepatocyte trasplantation in Spain creating a new research work on transplant program.
Keywords:
Liver transplantation
Hepatocyte transplantation
Hepatocyte
Inborn errors of liver metabolism
Liver failure
Resumen
El trasplante hepático es el único tratamiento efectivo existente para las enfermedades hepáticas en fase terminal. La desproporción entre la demanda y la oferta de órganos constituye su principal limitación y plantea la necesidad de buscar alternativas al trasplante hepático.
El trasplante celular hepático o trasplante de hepatocitos humanos constituye, en el momento actual, la mejor opción terapéutica sustitutiva. Consiste en trasplantar hepatocitos humanos totalmente diferenciados a un órgano receptor, en cantidad suficiente para que éstos sobrevivan y restauren la función hepática normal, basándose en la capacidad de regeneración hepática. Este tratamiento está en fase clinicoexperimental, y se ha realizado en pacientes con errores congénitos del metabolismo, fallo hepático fulminante y fallo hepático agudo o crónico como puente al trasplante convencional.
En el Hospital La Fe de Valencia hemos puesto en marcha y llevado a cabo el primer trasplante celular hepático en España, por tanto, esto abre una nueva línea de trabajo dentro del Programa de Trasplante Hepático.
Palabras clave:
Trasplante hepático
Trasplante celular hepático
Hepatocitos
Errores congénitos del metabolismo
Fallo hepático
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References
[1.]
S.C. Strom, R.A. Fisher, M.T. Thompson, A.J. Sanyal, P.E. Cole, J.M. Ham, et al.
Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure.
Transplantation, 63 (1997), pp. 559-569
[2.]
F. Smets, M. Najimi, E.M. Sokal.
Cell transplantation in the treatment of liver diseases.
Pediatr Transplant, 12 (2008), pp. 6-13
[3.]
S.C. Strom, R.A. Fisher, W.S. Rubinstein, J.A. Barranger, R.B. Towbin, M. Charron, et al.
Transplantation of human hepatocytes.
Transplant Proc, 29 (1997), pp. 2103-2106
[4.]
A. Dhawan, R.R. Mitry, R.D. Hughes.
Hepatocyte transplantation for metabolic disorders, experience at King's College Hospital and review of literature.
Acta Gastroenterol Belg, 68 (2005), pp. 457-460
[5.]
R.A. Fisher, S.C. Strom.
Human hepatocyte transplantation: worldwide results.
Transplantation, 82 (2006), pp. 441-449
[6.]
M. Grossman, S.E. Raper, K. Kozarsky, E.A. Stein, J.F. Engelhardt, D. Muller, et al.
Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia.
Nat Genet, 6 (1994), pp. 335-341
[7.]
S.M. Riordan, R. Williams.
Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis.
J Gastroenterol Hepatol, 14 (1999), pp. 757-770
[8.]
M. Muraca, G. Gerunda, D. Neri, M.T. Vilei, A. Granato, P. Feltracco, et al.
Hepatocyte transplantation as a treatment for glycogen storage disease type 1a.
Lancet, 359 (2002), pp. 317-318
[9.]
B.M. Bilir, D. Guinette, F. Karrer, D.A. Kumpe, J. Krysl, J. Stephens, et al.
Hepatocyte transplantation in acute liver failure.
Liver Transplantation, 6 (2000), pp. 32-40
[10.]
I.J. Fox, J.R. Chowdhury, S.S. Kaufman, T.C. Goertzen, N.R. Chowdhury, P.I. Warkentin, et al.
Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation.
N Engl J Med, 338 (1998), pp. 1422-1426
[11.]
C.M. Habibullah, I.H. Syed, A. Qamar, Z. Taher-Uz.
Human fetal hepatocyte transplantation in patients with fulminant hepatic failure.
Transplantation, 58 (1994), pp. 951-952
[12.]
A. Dhawan, R.R. Mitry, R.D. Hughes, S. Lehec, C. Terry, S. Bansal, et al.
Hepatocyte transplantation for inherited factor VII deficiency.
Transplantation, 78 (2004), pp. 1812-1814
[13.]
G. Ambrosino, S. Varotto, S.C. Strom, G. Guariso, E. Franchin, D. Miotto, et al.
Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1.
Cell Transplant, 14 (2005), pp. 151-157
[14.]
N. Navarro-Álvarez, A. Soto-Gutiérrez, N. Kobayashi.
Hepatocyte transplantation: a step forward.
Curr Opin Organ Transplant, 12 (2008), pp. 652-658
[15.]
A.A. Darwish, E. Sokal, X. Stéphenne, M. Najimi, J. De Ville de Goyet, R. Reding.
Permanent access to the portal system for cellular transplantation using an implantable port device.
Liver Transpl, 10 (2004), pp. 1213-1215
[16.]
S.C. Strom, J. Roy-Chowdhury, I.J. Fox.
Hepatocyte transplantation for the treatment of human disease.
Sem Liver Dis, 19 (1999), pp. 39-48
[17.]
E.M. Sokal.
Liver transplantation for inborn errors of liver metabolism.
J Inherit Metab Dis, 29 (2006), pp. 426-430
[18.]
S.P. Horslen, T.C. McCowan, T.C. Goertzen, P.I. Warkentin, H.B. Cai, S.C. Strom, et al.
Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder.
Pediatrics, 111 (2003), pp. 1262-1267
[19.]
X. Stepehenne, M. Najimi, F. Smets, R. Reding, J. De Ville de Goyet, E.M. Sokal.
Cryopreserved liver cell transplantation controls ornithine transcarbamylase deficient patient while awaiting liver transplantation.
Am J Transplant, 5 (2005), pp. 2058-2061
[20.]
A. Dhawan, R.R. Mitry, R.D. Hughes.
Hepatocyte transplantation for liver-based metabolic disorders.
J Inherit Metab Dis, 29 (2006), pp. 431-435
[21.]
E.M. Sokal, F. Smets, A. Bourgois, L. Van Maldergem, J.P. Buts, R. Reding, et al.
Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up.
Transplantation, 76 (2003), pp. 735-738
[22.]
B. Bilir, J.D. Durham, J. Kristal.
Transjugular intraportal transplantation of cryopreserved human hepatocytes in a patient with acute liver failure.
Hepatology, 24 (1996), pp. 728
[23.]
H.E. Soriano, R.P. Wood, D.C. Kang.
Hepatocellular transplantation (HCT) in children with fulminant liver failure (FLF).
Hepatology, 26 (1997), pp. 239A
[24.]
A.A. Khan, A. Habeeb, N. Parveen, B. Naseem, R.P. Babu, A.K. Capoor, et al.
Peritoneal transplantation of human fetal hepatocytes for the treatment of acute fatty liver of pregnancy: a case report.
Trop Gastroenterol, 25 (2004), pp. 141-143
[25.]
U. Baccarani, G.L. Adani, A. Sanna, C. Avellini, M. Sainz-Barriga, D. Lorenzin, et al.
Portal vein trombosis after intraportal hepatocytes transplantation in a liver transplant recipient.
Transpl International, 18 (2005), pp. 750-754
[26.]
K.W. Lee, J.H. Lee, S.W. Shin, S.J. Kim, J.W. Joh, D.H. Lee, et al.
Hepatocyte transplantation for glycogen storage disease type Ib.
Cell Transplant, 16 (2007), pp. 629-637
[27.]
K.J. Allen, H.E. Soriano.
Liver cell transplantation: the road to clinical application.
J Lab Clin Med, 138 (2001), pp. 298-312
[28.]
R.D. Hughes, R.R. Mitry, A. Dhawan.
Hepatocyte transplantation for metabolic liver disease: UK experience.
J R Soc Med, 98 (2005), pp. 341-345
[29.]
X. Stéphenne, M. Najimi, C. Sibille, M.C. Nassogne, F. Smets, E.M. Sokal.
Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency.
Gastroenterology, 130 (2006), pp. 1317-1323
[30.]
X. Stéphenne, M. Najimi, F. Smets, E.M. Sokal, R. Reding, J.V. Goyet.
Cryopreserved liver cell transplantation controls ornithine transcarbamylase deficient patient while awaiting liver transplantation.
Case Report Am J Trans, 5 (2005), pp. 2058-2061
[31.]
P.A. Lysy, M. Najimi, X. Stephenne, A. Bourgois, F. Smets, E. Sokal.
Liver cell transplantation for Crigler Najjar syndrome type I: update and perspectives.
World J Gastroenterol, 14 (2008), pp. 3464-3470
[32.]
A. Zimmermann.
Regulation of liver regeneration.
Nephrol Dial, 19 (2004), pp. 6-10
[33.]
M. Ito, H. Nagata, S. Miyakawa, I.J. Fox.
Review of hepatocyte transplantation.
J Hepatobiliary Pancreat Surg, 6 (2008), pp. 34-38
[34.]
R. Tabú.
Liver regeneration: from myth to mechanism.
Nature Reviews Mol Cel, 5 (2004), pp. 836-847
[35.]
R.B. Howard, A.K. Christensen, F.A. Gibbs, L.A. Pessch.
The enzimatic preparation of isolated intact parenchymal cells from rat liver.
J Cell Biol, 35 (1967), pp. 675-678
[36.]
Eiseman B. Treatment of liver failure. In: Read AE 8Ed. Colston Papers No. 19. The Liver. London: Butterworths; 1967. p. 279–85.
[37.]
A. Serralta, M.T. Donato, F. Orbis, J.V. Castell, J. Mir, M.J. Gómez-Lechón.
Functionality of cultured human hepatocytes from elective samples, cadaveric grafts and hepatectomies.
Toxicol In Vitro, 17 (2003), pp. 769-774
[38.]
D.E. Sutherland, M. Numata, A.J. Matas, R.L. Simmons, J.S. Najarian.
Hepatocellular transplantation in acute liver failure.
Surgery, 82 (1977), pp. 124-132
[39.]
T.A. Ahmad, H. Fujioka, S. Eguchi, K. Yanaga, Y. Kamohara, J. Furui, et al.
Long-term effect of hepatocyte transplantation on fulminant hepatic failure in rats.
Hepatogastroenterology, 50 (2003), pp. 467-471
[40.]
T.A. Ahmad, S. Eguchi, K. Yanaga, S. Miyamoto, Y. Kamohara, H. Fujioka, et al.
Role of intrasplenic hepatocyte transplantation in improving survival and liver regeneration after hepatic resection in cirrhotic rats.
Cell Transplant, 11 (2002), pp. 399-402
[41.]
N. Kobayashi, M. Ito, J. Nakamura, J. Cai, C. Gao, J.M. Hammel, et al.
Hepatocyte transplantation in rats with decompensated cirrhosis.
Hepatology, 31 (2000), pp. 851-857
[42.]
M. Mito, M. Kusano, M. Sawa.
Hepatocyte transplantation for hepatic failure.
Transplantat Reviews, 73 (1993), pp. 5-43
[43.]
J.M. De Vree, R. Ottenhoff, P.J. Bosma, A.J. Smith, J. Aten, R.P. Oude Elferink.
Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis.
Gastroenterology, 119 (2000), pp. 1720-1730
[44.]
D. Palmes, A.K. Qayumi, H.U. Spiegel.
Liver bridging techniques in the treatment of acute liver failure.
J Invest Surg, 13 (2000), pp. 299-311
[45.]
B.M. Bilir, D. Guenette, A. Ostrowska.
Percutaneous hepatocyte transplantation (PHT) in liver failure.
Hepatology, 26 (1997), pp. 494
[46.]
N. Fausto, J.S. Campbell, K.J. Riehle.
Liver regeneration.
Hepatology, 43 (2006), pp. S45-S53
[47.]
R.R. Mitry, R.D. Hughes, A. Dhawan.
Progress in human hepatocytes: isolation, culture & cryopreservation.
Semin Cell Dev Biol, 13 (2002), pp. 463-467
[48.]
M.J. Gómez-Lechón, T. Donato, X. Ponsoda, R. Fabra, R. Trullenque, J.V. Castell.
Isolation, culture and use of human hepatocytes in drug research.
Vitro methods in pharmaceitical research, Academic Press, (1997),
[49.]
M. Ott, M. Barthold, K. Alexandrova.
Clinical applications of human hepatocytes isolated under CGMP conditions. 40th annual meeting of the European Association for the study of the liver.
J Hepatol, 42 (2005), pp. 1-283
[50.]
M. Mito, M. Kusano.
Hepatocyte transplantation in man.
Cell Transplant, 2 (1993), pp. 65-74
[51.]
M. Mito, M. Kusano, Y. Kawaura.
Hepatocyte transplantation in man.
Transplant Proc, 24 (1992), pp. 3052-3053
[52.]
G.L. Bumgardner, D. Gao, J. Li, A. Bickerstaff, C.G. Orosz.
MHCidentical heart and hepatocyte allografts evoke opposite immune responses within the same host.
Transplantation, 74 (2002), pp. 855-864
[53.]
M.T. Donato, A. Lahoz, N. Jiménez, G. Pérez, A. Serralta, J. Mir, et al.
Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts.
Drug Metab Dispos, 34 (2006), pp. 1556-1562
[54.]
R.K. Sterling, R.A. Fisher.
Liver transplantation: living donor, hepatocyte, and xenotransplantation.
Current future treatment therapies for liver disease. Clinics in liver disease,
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