title: In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation.
abstract: Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P = 0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control = 6.3 ± 0.9; HOC = 3.5 ± 1.5; P = 0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation.
authors.affiliation: Liaocheng People's Hospital, Department of Hepatobiliary Surgery, LiaochengShandong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: J H
authors.initials: JH
authors.lastname: Ran
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: T X
authors.initials: TX
authors.lastname: Gao
authors.forename: B Y
authors.initials: BY
authors.lastname: Guo
authors.forename: X H
authors.initials: XH
authors.lastname: Li
authors.forename: Z H
authors.initials: ZH
authors.lastname: Liu
authors.forename: G J
authors.initials: GJ
authors.lastname: Liu
authors.forename: Y C
authors.initials: YC
authors.lastname: Gao
authors.forename: X L
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000175:diagnosis; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology*; D007150:Immunohistochemistry; D008099:Liver / Q000033:anatomy & histology / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D061251:Primary Cell Culture; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015996:Survival Rate
references.citation: Am J Pathol. 1991 Sep;139(3):535-52
references.pmid: 1716045
references.citation: Eur J Neurosci. 2007 Nov;26(10):2979-88
references.pmid: 18001292
references.citation: Hepatology. 1998 Feb;27(2):433-45
references.pmid: 9462642
references.citation: Transplantation. 2007 Mar 27;83(6):694-9
references.pmid: 17414700
references.citation: Artif Organs. 2001 Jul;25(7):513-21
references.pmid: 11493271
references.citation: FEBS Lett. 2000 Mar 31;470(3):325-30
references.pmid: 10745090
references.citation: Curr Opin Organ Transplant. 2010 Feb;15(1):49-51
references.pmid: 19949334
references.citation: Carcinogenesis. 1987 Nov;8(11):1737-40
references.pmid: 3664968
references.citation: Gastroenterology. 2001 Feb;120(2):534-44
references.pmid: 11159894
references.citation: Immunol Cell Biol. 2005 Aug;83(4):364-74
references.pmid: 16033531
references.citation: J Surg Res. 2012 Jul;176(1):317-20
references.pmid: 22172136
references.citation: Am J Pathol. 2001 Apr;158(4):1313-23
references.pmid: 11290549
references.citation: J Hepatol. 2005;42 Suppl(1):S75-84
references.pmid: 15777575
references.citation: Am J Pathol. 1997 Aug;151(2):353-9
references.pmid: 9250149
references.citation: Semin Liver Dis. 2003 Nov;23(4):363-72
references.pmid: 14722813
references.citation: Semin Cell Dev Biol. 2002 Dec;13(6):405-9
references.pmid: 12468240
references.citation: Leuk Lymphoma. 2007 May;48(5):885-91
references.pmid: 17487731
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11881-8
references.pmid: 12902545
references.citation: Am J Pathol. 1994 Aug;145(2):409-22
references.pmid: 8053498
references.citation: J Hepatol. 2007 Jun;46(6):1055-63
references.pmid: 17434228
references.citation: Abdom Imaging. 2007 May-Jun;32(3):339-47
references.pmid: 16967253
references.citation: Mech Dev. 2003 Jan;120(1):117-30
references.pmid: 12490302
references.citation: Front Med. 2011 Mar;5(1):106-10
references.pmid: 21681683
references.citation: World J Gastroenterol. 2009 Feb 7;15(5):552-60
references.pmid: 19195056
references.citation: Histochem Cell Biol. 2007 Sep;128(3):217-26
references.pmid: 17661067
references.citation: Hepatology. 2004 May;39(5):1353-61
references.pmid: 15122764