title: Hepatocyte transplantation program: Lessons learned and future strategies.
abstract: This review aims to share the lessons we learned over time during the setting of the hepatocyte transplantation (HT) program at the Hepatic Cell Therapy Unit at Hospital La Fe in Valencia. New sources of liver tissue for hepatocyte isolation have been explored. The hepatocyte isolation and cryopreservation procedures have been optimized and quality criteria for assessment of functionality of hepatocyte preparations and suitability for HT have been established. The results indicate that: (1) Only highly viable and functional hepatocytes allow to recover those functions lacking in the native liver; (2) Organs with steatosis (≥ 40%) and from elderly donors are declined since low hepatocyte yields, viability and cell survival after cryopreservation, are obtained; (3) Neonatal hepatocytes are cryopreserved without significant loss of viability or function representing high-quality cells to improve human HT; (4) Cryopreservation has the advantage of providing hepatocytes constantly available and of allowing the quality evaluation and suitability for transplantation; and (5) Our results from 5 adults with acute liver failure and 4 from children with inborn metabolic diseases, indicate that HT could be a very useful and safe cell therapy, as long as viable and metabolically functional human hepatocytes are used.
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: Eugenia Pareja
authors.initials: EP
authors.lastname: Ibars
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cortes
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Tolosa
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Gómez-Lechón
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: Slivia
authors.initials: S
authors.lastname: López
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Castell
authors.affiliation: Eugenia Pareja Ibars, Laia Tolosa, Maria Jose Gomez-Lechón, Slivia López, Jose Vicente Castell, Jose Mir, Unidad de Terapia Celular Hepatica, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Mir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival; D015925:Cryopreservation / Q000379:methods; D004059:Diffusion of Innovation; D046148:Donor Selection; D005260:Female; D005544:Forecasting; D006085:Graft Survival; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery*; D008875:Middle Aged; D018579:Patient Selection; D012307:Risk Factors; D016896:Treatment Outcome
keywords: Cell therapy; Cryopreservation; Hepatocyte isolation; Hepatocyte transplantation; Inborn errors of metabolism; Neonatal hepatocytes
references.citation: Transplant Proc. 2010 Oct;42(8):2959-61
references.pmid: 20970581
references.citation: Cell Transplant. 2008;17(8):887-97
references.pmid: 19069632
references.citation: Cir Esp. 2010 Jul;88(1):3-11
references.pmid: 20510402
references.citation: Liver Int. 2011 Sep;31(8):1231-8
references.pmid: 22093411
references.citation: Lancet. 2002 Jan 26;359(9303):317-8
references.pmid: 11830200
references.citation: Cir Esp. 2010 Mar;87(3):139-47
references.pmid: 20079490
references.citation: Cell Tissue Bank. 2000;1(1):55-68
references.pmid: 15256968
references.citation: Cell Transplant. 2008;17(10-11):1211-9
references.pmid: 19181215
references.citation: Vopr Onkol. 1975;21(2):75-9
references.pmid: 805497
references.citation: Cryobiology. 2006 Oct;53(2):149-59
references.pmid: 16793034
references.citation: J Cell Sci. 1976 Nov;22(2):455-65
references.pmid: 794074
references.citation: J Intern Med. 2009 Oct;266(4):339-57
references.pmid: 19765179
references.citation: Cell Transplant. 2009;18(7):777-86
references.pmid: 19796496
references.citation: Cell Transplant. 2012;21(1):23-37
references.pmid: 21669032
references.citation: Nat Rev Gastroenterol Hepatol. 2010 May;7(5):288-98
references.pmid: 20368738
references.citation: Cell Transplant. 2005;14(8):585-94
references.pmid: 16355567
references.citation: Cell Transplant. 2005;14(10):837-43
references.pmid: 16454358
references.citation: Eur Surg Res. 2013;50(3-4):273-81
references.pmid: 23796722
references.citation: Cir Esp. 2014 Feb;92(2):74-81
references.pmid: 24007980
references.citation: Acta Stomatol Belg. 1991 Jun;88(2):85-92
references.pmid: 1822056
references.citation: Semin Cell Dev Biol. 2002 Dec;13(6):463-7
references.pmid: 12468248
references.citation: Cell Transplant. 2010;19(11):1487-92
references.pmid: 20587150
references.citation: Gastroenterology. 2000 Dec;119(6):1720-30
references.pmid: 11113093
references.citation: Transplantation. 2004 Dec 27;78(12):1812-4
references.pmid: 15614156
references.citation: Am J Transplant. 2005 Aug;5(8):2058-61
references.pmid: 15996260
references.citation: J Cell Biol. 1969 Dec;43(3):506-20
references.pmid: 4900611
references.citation: J Cell Biol. 1967 Dec;35(3):675-84
references.pmid: 4294245
references.citation: Liver Transpl. 2010 Feb;16(2):229-37
references.pmid: 20104500
references.citation: Cell Transplant. 2005;14(10):845-53
references.pmid: 16454359
references.citation: Cell Transplant. 2012;21(1):1-10
references.pmid: 21457616
references.citation: Transplantation. 2011 Jun 27;91(12):1340-6
references.pmid: 21516066
references.citation: Transpl Int. 2005 Jun;18(6):750-4
references.pmid: 15910305
references.citation: Transpl Immunol. 2004 Apr;12(3-4):273-88
references.pmid: 15157921
references.citation: Arh Hig Rada Toksikol. 1992 Dec;43(4):359-64
references.pmid: 1297312
references.citation: J Intern Med. 2012 Sep;272(3):201-23
references.pmid: 22789058
references.citation: Cell Transplant. 2014;23(10):1229-42
references.pmid: 23803290
references.citation: Pediatrics. 2003 Jun;111(6 Pt 1):1262-7
references.pmid: 12777539
references.citation: N Engl J Med. 1998 May 14;338(20):1422-6
references.pmid: 9580649
references.citation: J Neuroradiol. 1991;18(3):277-85
references.pmid: 1765813
references.citation: Arch Biochem Biophys. 2000 Apr 1;376(1):109-16
references.pmid: 10729196
references.citation: Cell Transplant. 2012;21(10):2267-82
references.pmid: 23231960
references.citation: Surgery. 1977 Jul;82(1):124-32
references.pmid: 327598
references.citation: Transplantation. 2006 Aug 27;82(4):441-9
references.pmid: 16926585
references.citation: J Gastroenterol Hepatol. 1999 Aug;14(8):757-70
references.pmid: 10482426
references.citation: Transplantation. 2012 Feb 27;93(4):342-7
references.pmid: 22082820
references.citation: Cell Transplant. 2010;19(1):21-8
references.pmid: 19796502
references.citation: Vestn Akad Med Nauk SSSR. 1990;(5):10-4
references.pmid: 2389594
references.citation: Liver Transpl. 2015 Jun;21(6):801-11
references.pmid: 25821167
references.citation: Transplantation. 2004 May 27;77(10):1614-6
references.pmid: 15239631
references.citation: Nat Rev Mol Cell Biol. 2004 Oct;5(10):836-47
references.pmid: 15459664
references.citation: Hepatology. 2000 Apr;31(4):851-7
references.pmid: 10733539
references.citation: Arch Dis Child. 1991 Sep;66(9):1101-2
references.pmid: 1929530
references.citation: Cell Transplant. 2005;14(2-3):151-7
references.pmid: 15881424
references.citation: Liver Transpl. 2000 Jan;6(1):32-40
references.pmid: 10648575
references.citation: Toxicol In Vitro. 2003 Oct-Dec;17(5-6):769-74
references.pmid: 14599475
references.citation: Eur J Surg. 1991 Feb;157(2):109-12
references.pmid: 1676301
references.citation: Drug Metab Dispos. 2005 Jan;33(1):108-14
references.pmid: 15448115
references.citation: Transplant Proc. 1995 Oct;27(5):2893-4
references.pmid: 7482956
references.citation: Semin Liver Dis. 1999;19(1):39-48
references.pmid: 10349682
references.citation: Drug Metab Dispos. 2000 Nov;28(11):1321-6
references.pmid: 11038160
references.citation: Liver Transpl. 2010 Aug;16(8):974-82
references.pmid: 20677288