NeoHepatocytes from alcoholics and controls express hepatocyte markers and display reduced fibrogenic TGF-β/Smad3 signaling: Advantage for cell transplantation?

Alcoholism: Clinical and Experimental Research

Volumn 34, Issue 4, 2010, Pages 708-718

  Ehnert, Sabrina ^a   Knobeloch, Daniel ^b,c   Blankenstein, Antje ^b,c   Müller, Alexandra ^d   Böcker, Ulrich ^d   Gillen, Sonja ^a   Friess, Helmut ^a   Thasler, Wolfgang E ^e   Dooley, Steven ^d   Nussler, Andreas K ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b Department of General ^*  (Australia)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d UNIVERSITY OF HEIDELBERG   (Germany)

^e UNIVERSITY OF MUNICH   (Germany)

Author keywords

Alcoholic Liver Disease; Cell Transplantation; Hepatocytes; NeoHepatocytes; Smad3; TGF

Indexed keywords

ALCOHOL; ALCOHOL DEHYDROGENASE; CELL MARKER; CONNECTIVE TISSUE GROWTH FACTOR; CYTOCHROME P450; CYTOKERATIN 18; DNA; FIBRONECTIN; GLUCOSE; INSULIN; SMAD1 PROTEIN; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UREA;

ALCOHOL LIVER CIRRHOSIS; ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; CELL DIFFERENTIATION; CELL TYPE; CHRONIC LIVER DISEASE; CONTROLLED STUDY; DNA DETERMINATION; DOWN REGULATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HEPATOCYTE TRANSPLANTATION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOFLUORESCENCE TEST; LIPID STORAGE; LIVER CELL; MONOCYTE; NEOHEPATOCYTE; NUCLEOTIDE SEQUENCE; PHOTOMETRY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

ALCOHOLISM; BIOLOGICAL MARKERS; CELL TRANSPLANTATION; CELLS, CULTURED; CONNECTIVE TISSUE GROWTH FACTOR; FIBRONECTINS; GENE EXPRESSION REGULATION; HEPATOCYTES; HUMANS; LIVER CIRRHOSIS, ALCOHOLIC; MONOCYTES; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TRANSPLANTATION, AUTOLOGOUS;

RATTUS;

EID: 77949957393     PISSN: 01456008     EISSN: 15300277     Source Type: Journal    
DOI: 10.1111/j.1530-0277.2009.01140.x     Document Type: Article

References (38)

1. Akhurst RJ, Derynck R (2001) TGF-beta signaling in cancer-a double-edged sword. Trends Cell Biol 11 : S44 S51.
2. Albanis E, Friedman SL (2001) Hepatic fibrosis. Pathogenesis and principles of therapy. Clin Liver Dis 5 : 315 334. v-vi.
3. Arendt E, Ueberham U, Bittner R, Gebhardt R, Ueberham E (2005) Enhanced matrix degradation after withdrawal of TGF-beta1 triggers hepatocytes from apoptosis to proliferation and regeneration. Cell Prolif 38 : 287 299.
4. Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115 : 209 218.
5. Benyon RC, Iredale JP (2000) Is liver fibrosis reversible? Gut 46 : 443 446.
6. Bosetti C, Levi F, Lucchini F, Zatonski WA, Negri E, La Vecchia C (2007) Worldwide mortality from cirrhosis: an update to 2002. J Hepatol 46 : 827 839.
7. Chen WX, Li YM, Yu CH, Cai WM, Zheng M, Chen F (2002) Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease. World J Gastroenterol 8 : 379 381.
8. Cheon SS, Wei Q, Gurung A, Youn A, Bright T, Poon R, Whetstone H, Guha A, Alman BA (2006) Beta-catenin regulates wound size and mediates the effect of TGF-beta in cutaneous healing. FASEB J 20 : 692 701.
9. Dooley S, Hamzavi J, Breitkopf K, Wiercinska E, Said HM, Lorenzen J, Ten Dijke P, Gressner AM (2003) Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats. Gastroenterology 125 : 178 191.
10. Dooley S, Hamzavi J, Ciuclan L, Godoy P, Ilkavets I, Ehnert S, Ueberham E, Gebhardt R, Kanzler S, Geier A, Breitkopf K, Weng H, Mertens PR (2008) Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology 135 : 642 659.
11. Ehnert S, Nussler AK, Lehmann A, Dooley S (2008) Blood monocyte-derived neohepatocytes as in vitro test system for drug metabolism. Drug Metab Dispos 36 : 1922 1929.
12. Friedman SL (2008) Mechanisms of hepatic fibrogenesis. Gastroenterology 134 : 1655 1669.
13. Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, Nakamura Y, Kikuchi A, Miyazono K, Kato M (2001) Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway. Mol Cell Biol 21 : 5132 5141.
14. Gabelein G, Nussler AK, Morgott F, Ping Y, Nussler N, Neuhaus P, Glanemann M (2008) Intrasplenic or subperitoneal hepatocyte transplantation to increase survival after surgically induced hepatic failure? Eur Surg Res 41 : 253 259.
15. Geerts A, Eliasson C, Niki T, Wielant A, Vaeyens F, Pekny M (2001) Formation of normal desmin intermediate filaments in mouse hepatic stellate cells requires vimentin. Hepatology 33 : 177 188.
16. Glanemann M, Gaebelein G, Nussler N, Hao L, Kronbach Z, Shi B, Neuhaus P, Nussler AK (2009) Transplantation of monocyte-derived hepatocyte-like cells (NeoHeps) improves survival in a model of acute liver failure. Ann Surg 249 : 149 154.
17. Gressner OA, Lahme B, Demirci I, Gressner AM, Weiskirchen R (2007) Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes. J Hepatol 47 : 699 710.
18. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S (2002) Roles of TGF-beta in hepatic fibrosis. Front Biosci 7 : d793 d807.
19. Hengstler JG, Brulport M, Schormann W, Bauer A, Hermes M, Nussler AK, Fandrich F, Ruhnke M, Ungefroren H, Griffin L, Bockamp E, Oesch F, von Mach MA (2005) Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol 1 : 61 74.
20. Higuchi H, Gores GJ (2003) Mechanisms of liver injury: an overview. Curr Mol Med 3 : 483 490.
21. Horiguchi K, Shirakihara T, Nakano A, Imamura T, Miyazono K, Saitoh M (2009) Role of Ras signaling in the induction of snail by transforming growth factor-beta. J Biol Chem 284 : 245 253.
22. Kornblihtt AR, Pesce CG, Alonso CR, Cramer P, Srebrow A, Werbajh S, Muro AF (1996) The fibronectin gene as a model for splicing and transcription studies. FASEB J 10 : 248 257.
23. Maher JJ (2001) Interactions between hepatic stellate cells and the immune system. Semin Liver Dis 21 : 417 426.
24. Nagata H, Ito M, Cai J, Edge AS, Platt JL, Fox IJ (2003a) Treatment of cirrhosis and liver failure in rats by hepatocyte xenotransplantation. Gastroenterology 124 : 422 431.
25. Nagata H, Ito M, Shirota C, Edge A, McCowan TC, Fox IJ (2003b) Route of hepatocyte delivery affects hepatocyte engraftment in the spleen. Transplantation 76 : 732 734.
26. Nussler A, Konig S, Ott M, Sokal E, Christ B, Thasler W, Brulport M, Gabelein G, Schormann W, Schulze M, Ellis E, Kraemer M, Nocken F, Fleig W, Manns M, Strom SC, Hengstler JG (2006) Present status and perspectives of cell-based therapies for liver diseases. J Hepatol 45 : 144 159.
27. Nussler AK, Nussler NC, Merk V, Brulport M, Schormann W, Yao P, Hengstler JG (2009) The holy grail of hepatocyte culturing and therapeutic use, in Strategies in Regenerative Medicine (Santin M ed pp. 283 320. Springer Science + Business Media, New York.
28. Ott M, Schmidt HH, Cichon G, Manns MP (2000) Emerging therapies in hepatology: liver-directed gene transfer and hepatocyte transplantation. Cells Tissues Organs 167 : 81 87.
29. Ruhnke M, Nussler AK, Ungefroren H, Hengstler JG, Kremer B, Hoeckh W, Gottwald T, Heeckt P, Fandrich F (2005a) Human monocyte-derived neohepatocytes: a promising alternative to primary human hepatocytes for autologous cell therapy. Transplantation 79 : 1097 1103.
30. Ruhnke M, Ungefroren H, Nussler A, Martin F, Brulport M, Schormann W, Hengstler JG, Klapper W, Ulrichs K, Hutchinson JA, Soria B, Parwaresch RM, Heeckt P, Kremer B, Fandrich F (2005b) Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 128 : 1774 1786.
31. Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414 : 799 806.
32. Sokal EM, Smets F, Bourgois A, Van Maldergem L, Buts JP, Reding R, Bernard Otte J, Evrard V, Latinne D, Vincent MF, Moser A, Soriano HE (2003) Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up. Transplantation 76 : 735 738.
33. Stickel F, Urbaschek R, Schuppan D, Poeschl G, Oesterling C, Conradt C, McCuskey RS, Simanowski UA, Seitz HK (2001) Serum collagen type VI and XIV and hyaluronic acid as early indicators for altered connective tissue turnover in alcoholic liver disease. Dig Dis Sci 46 : 2025 2032.
34. Street CN, Rajotte RV, Korbutt GS (2003) Stem cells: a promising source of pancreatic islets for transplantation in type 1 diabetes. Curr Top Dev Biol 58 : 111 136.
35. Strom S, Fisher R (2003) Hepatocyte transplantation: new possibilities for therapy. Gastroenterology 124 : 568 571.
36. Ueberham E, Arendt E, Starke M, Bittner R, Gebhardt R (2004) Reduction and expansion of the glutamine synthetase expressing zone in livers from tetracycline controlled TGF-beta1 transgenic mice and multiple starved mice. J Hepatol 41 : 75 81.
37. Weng HL, Ciuclan L, Liu Y, Hamzavi J, Godoy P, Gaitantzi H, Kanzler S, Heuchel R, Ueberham U, Gebhardt R, Breitkopf K, Dooley S (2007) Profibrogenic transforming growth factor-beta/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes. Hepatology 46 : 1257 1270.
38. Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83 : 835 870.