|
|
|
| Transplantation of a hepatocye cell line Chang liver cell improves the survival of acute liver faliure |
| YANG Tao1, WANG Jing2, LI Yuming1, YU Xingquan1, SUN Qinglei1, ZHU Jun1, SONG Bingtan1 |
1 Department of Gastrointestinal Surgical,Hospital of Binzhou Medical University,Binzhou 256603,P.R.China;
2 Department of Dermatology,Hospital of Binzhou Medical University |
|
|
|
|
Abstract Objective To verify the function of hepatocytes by in vitro experiments and in vivo acute hepatic failure model and search for a novel cell source for liver support system.Methods the expressions of specific hepatocyte markers were detected by western-blotting and laser confocal microscopy to evaluate the hepatocytic function of Chang Liver cells in vitro. Related gene expression of hepatic function was detected by RT-PCR.The acute liver failure (ALF) model was established by 90% partial hepatectomy.Chang Liver cells were intra-splenically implanted 24 hours before the surgery and the serum samples were collected per 24 hours to test the liver functions. And the survivals were assessed.Results In vitro, conspicuous expression of hepatocytic markers,such as albumin (ALB),uridine diphosphate glucuronosyltransferase (UGT) and cytochrome P450 3A4 (CYP3A4) in Chang Liver cells.RT-PCR also exhibited the expression of related genes at mRNA level.In vivo,the survival of rats receiving Chang Liver cells was significantly improved and reached 40% against 0% in controls.Liver functions of rats receiving Chang Liver cells were also significantly improved 24 h after ALF,which was evidenced by the decreased levels of alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin and alkaline phosphates (ALP) in blood samples of rats implanted with Chang liver cells.Conclusion Chang Liver cells express hepatocytic markers and significantly improve liver function and survival after ALF, which can serve for liver support systems cells.
|
|
Received: 15 December 2017
|
|
|
|
|
|
[1] Bower W A,Johns M,Margolis H S,et al.Population-based surveillance for acute liver failure[J] .Am J Gastroenterol,2007,102(11):2459-2463.
[2] Miyamura T,Kanda T,Minemura S,et al. Acute liver failure associated with propylthiouracil in a pregnant 26-year-old woman[J] .Case Rep Gastroenterol,2013,7(2):240-244.
[3] Struecker B,Raschzok N,Sauer I M.Liver support strategies:cutting-edge technologies[J] .Nat Rev Gastroenterol Hepatol,2014,11(3):166-176.
[4] Du W B,Li L J,Huang J R,et al.Effects of artificial liver support system on patients with acute or chronic liver failure[J] .Transplant Proc,2005,37(10):4359-4364.
[5] Ikegami T,Soejima Y,Taketomi A,et al.Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors[J] .Transpl Int,2008,21(3):284-285.
[6] Cai J,Zhang M,Han T,et al.Characteristics of infection and its impact on short-term outcome in patients with acute-on-chronic liver failure[J] .Medicine (Baltimore),2017,96(37):e8057.
[7] Chan S C. Liver transplantation for fulminant hepatic failure:as early as necessary and as late as possible[J] .J Gastroenterol Hepatol,2011,26(1):3-4.
[8] Fonsato V,Herrera M B,Buttiglieri S,et al.Use of a rotary bioartificial liver in the differentiation of human liver stem cells[J] .Tissue Eng Part C Methods,2010,16(1):123-132.
[9] Erro E,Bundy J,Massie I,et al.Bioengineering the liver:scale-up and cool chain delivery of the liver cell biomass for clinical targeting in a bioartificial liver support system[J] . Biores Open Access, 2013, 2(1):1-11.
[10] Li L J,Du W B, Zhang Y M,et al.Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs[J] .J Hepatol,2006,44(2):317-324.
[11] Demetriou A A,Brown R S,Jr.,Busuttil R W,et al.Prospective, randomized,multicenter,controlled trial of a bioartificial liver in treating acute liver failure[J] .Ann Surg,2004,239(5):660-667;discussion 667-670.
[12] van de Kerkhove M P,Poyck P P,van Wijk A C,et al.Assessment and improvement of liver specific function of the AMC-bioartificial liver[J] .Int J Artif Organs,2005,28(6):617-630.
[13] van der Laan L J,Lockey C,Griffeth B C,et al.Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice[J] .Nature,2000,407(6800):90-94.
[14] Lin H,Yang G,Tan J,et al.Influence of decellularized matrix derived from human mesenchymal stem cells on their proliferation,migration and multi-lineage differentiation potential[J] .Biomaterials,2012,33(18):4480-4489.
[15] Ng C P,Sharif A R,Heath D E,et al.Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal stem cell ECM[J] .Biomaterials,2014,35(13):4046-4057.
[16] Chang R S.Continuous subcultivation of epithelial-like cells from normal human tissues[J] .Proc Soc Exp Biol Med,1954,87(2):440-443.
[17] Murphy W H,Landau B J.Clonal variation and interaction of cells with viruses[J] .Natl Cancer Inst Monogr,1962,7(2):249-271.
[18] Benn J,Su F,Doria M,et al.Hepatitis B virus HBx protein induces transcription factor AP-1 by activation ofextracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases[J] .J Virol,1996,70(8):4978-4985.
[19] Hughes R D,Yamada H,Gove C D,et al.Inhibitors of hepatic DNA synthesis in fulminant hepatic failure[J] .Dig Dis Sci,1991, 36(6):816-819.
[20] Saich R,Selden C,Rees M,et al.Characterization of pro-apoptotic effect of liver failure plasma on primary human hepatocytes and its modulation by molecular adsorbent recirculation system therapy[J] .Artif Organs,2007,31(9):732-742.
[21] Newsome P N,Tsiaoussis J,Masson S,et al.Serum from patients with fulminant hepatic failure causes hepatocyte detachment and apoptosis by a beta(1)-integrin pathway[J] .Hepatology,2004,40(3):636-645.
[22] Mitry R R,Hughes R D,Bansal S,et al.Effects of serum from patients with acute liver failure due to paracetamol overdose on human hepatocytes in vitro[J] .Transplant Proc,2005,37(5):2391-2394.
[23] Shi Q,Gaylor J D,Cousins R,et al.The effects of serum from patients with acute liver failure on the growth and metabolism of Hep G2 cells[J] .Artif Organs,1998,22(12):1023-1030.
[24] Hughes R D.Review of methods to remove protein-bound substances in liver failure[J] .Int J Artif Organs,2002,25(10):911-917.
[25] Yamada H,Toda G,Yoshiba M,et al.Humoral inhibitor of rat hepatocyte DNA synthesis from patients with fulminant liver failure[J] .Hepatology,1994,19(5):1133-1140.
[26] Nebert D W,Wikvall K,Miller W L. Human cytochromes P450 in health and disease[J] .Philos Trans R Soc Lond B Biol Sci,2013,368(1612):20120431.
[27] Lawrence B J,Devarapalli M,Madihally S V.Flow dynamics in bioreactors containing tissue engineering scaffolds[J] .Biotechnol Bioeng,2009,102(3):935-947.
[28] Safshekan F,Tafazzoli-Shadpour M,Shokrgozar M A,et al.Intermittent hydrostatic pressure enhances growth factor-induced chondroinduction of human adipose-derived mesenchymal stem cells[J] .Artif Organs,2012,36(12):1065-1071.
[29] Haghighipour N,Heidarian S,Shokrgozar M A,et al.Differential effects of cyclic uniaxial stretch on human mesenchymal stem cell into skeletal muscle cell[J] .Cell Biol Int,2012,36(7):669-675. |
|
|
|
