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Stem Cells and Chronic Liver Failure: Potential New Therapeutics

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Part of the book series: Clinical Gastroenterology ((CG))

Abstract

Fulminant hepatic failure is a disease with high mortality. Prior to orthotopic liver transplantation (OLT), the mortality rate was greater than 80%. With improved intensive care, however, several series report a survival rate of 60% (1). At present, standard therapy is liver transplantation and approximately 6% of OLTs performed in the United States are for fulminant hepatic failure.

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References

  1. Hoofnagle JH, Carithers RL, Jr., Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. Jan 1995;21(1):240–52.

    CAS  PubMed  Google Scholar 

  2. Fisher RA, Strom SC. Human hepatocyte transplantation: worldwide results. Transplantation. Aug 27 2006;82(4):441–9.

    PubMed  Google Scholar 

  3. Enns GM, Millan MT. Cell-based therapies for metabolic liver disease. Mol Genet Metab. Sep–Oct 2008;95(1–2):3–10.

    CAS  PubMed  Google Scholar 

  4. Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature. Jun 29 2006;441(7097):1068–1074.

    CAS  PubMed  Google Scholar 

  5. Gearhart J. New potential for human embryonic stem cells. Science. Nov 6 1998;282(5391):1061–1062.

    CAS  PubMed  Google Scholar 

  6. Barnabe-Heider F, Frisen J. Stem cells for spinal cord repair. Cell Stem Cell. Jul 3 2008;3(1):16–24.

    CAS  PubMed  Google Scholar 

  7. Kroon E, Martinson LA, Kadoya K, et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. Apr 2008;26(4):443–452.

    CAS  PubMed  Google Scholar 

  8. Stevens KR, Kreutziger KL, Dupras SK, et al. Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue. Proc Natl Acad Sci U S A. Sep 29 2009;106(39):16568–16573.

    CAS  PubMed  Google Scholar 

  9. Agarwal S, Holton KL, Lanza R. Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells. May 2008;26(5):1117–1127.

    CAS  PubMed  Google Scholar 

  10. Cho CH, Parashurama N, Park EY, et al. Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure. Faseb J. Mar 2008;22(3):898–909.

    CAS  PubMed  Google Scholar 

  11. Cai J, Zhao Y, Liu Y, et al. Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology. May 2007;45(5):1229–1239.

    CAS  PubMed  Google Scholar 

  12. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. Nov 30 2007;131(5):861–872.

    CAS  PubMed  Google Scholar 

  13. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. Aug 25 2006;126(4):663–676.

    PubMed  Google Scholar 

  14. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. Dec 21 2007;318(5858): 1917–1920.

    CAS  PubMed  Google Scholar 

  15. Woltjen K, Michael IP, Mohseni P, et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature. Apr 9 2009;458(7239):766–770.

    CAS  PubMed  Google Scholar 

  16. Kim JB, Greber B, Arauzo-Bravo MJ, et al. Direct reprogramming of human neural stem cells by OCT4. Nature. Oct 1 2009;461(7264):649–643.

    Google Scholar 

  17. Li W, Zhou H, Abujarour R, et al. Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells. Dec 2009;27(12):2992–3000.

    CAS  PubMed  Google Scholar 

  18. Conrad S, Renninger M, Hennenlotter J, et al. Generation of pluripotent stem cells from adult human testis. Nature. Nov 20 2008;456(7220):344–349.

    CAS  PubMed  Google Scholar 

  19. Kossack N, Meneses J, Shefi S, et al. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells. Jan 2009;27(1):138–149.

    CAS  PubMed  Google Scholar 

  20. Sullivan GJ, Hay DC, Park IH, et al. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology. Jan;51(1):329–335.

    Google Scholar 

  21. Si-Tayeb K, Noto FK, Nagaoka M, et al. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology. Jan;51(1):297–305.

    Google Scholar 

  22. Mishra B, Tang Y, Katuri V, et al. Loss of cooperative function of transforming growth factor-beta signaling proteins, smad3 with embryonic liver fodrin, a beta-spectrin, in primary biliary cirrhosis. Liver Int. Dec 2004;24(6):637–645.

    CAS  PubMed  Google Scholar 

  23. Zhao R, Duncan SA. Embryonic development of the liver. Hepatology. May 2005;41(5):956–967.

    CAS  PubMed  Google Scholar 

  24. Jung J, Zheng M, Goldfarb M, Zaret KS. Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science. Jun 18 1999;284(5422):1998–2003.

    CAS  PubMed  Google Scholar 

  25. Rossi JM, Dunn NR, Hogan BL, Zaret KS. Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev. Aug 1 2001;15(15):1998–2009.

    CAS  PubMed  Google Scholar 

  26. Shin D, Shin CH, Tucker J, et al. Bmp and Fgf signaling are essential for liver specification in zebrafish. Development. Jun 2007;134(11):2041–2050.

    CAS  PubMed  Google Scholar 

  27. Lemaigre F, Zaret KS. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev. Oct 2004;14(5):582–590.

    CAS  PubMed  Google Scholar 

  28. Alison MR. Liver stem cells: implications for hepatocarcinogenesis. Stem Cell Rev. 2005;1(3):253–260.

    CAS  PubMed  Google Scholar 

  29. Farber E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3'-methyl-4-dimethylaminoazobenzene. Cancer Res. Feb 1956;16(2):142–148.

    CAS  PubMed  Google Scholar 

  30. Smith PG, Tee LB, Yeoh GC. Appearance of oval cells in the liver of rats after long-term exposure to ethanol. Hepatology. Jan 1996;23(1):145–154.

    CAS  PubMed  Google Scholar 

  31. Smith PG, Yeoh GC. Chronic iron overload in rats induces oval cells in the liver. Am J Pathol. Aug 1996;149(2):389–398.

    CAS  PubMed  Google Scholar 

  32. Gordon GJ, Coleman WB, Hixson DC, Grisham JW. Liver regeneration in rats with retrorsine-induced hepatocellular injury proceeds through a novel cellular response. Am J Pathol. Feb 2000;156(2):607–619.

    CAS  PubMed  Google Scholar 

  33. Libbrecht L, Desmet V, Van Damme B, Roskams T. The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells. J Hepatol. Jul 2000;33(1):76–84.

    CAS  PubMed  Google Scholar 

  34. Yang S, Koteish A, Lin H, et al. Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease. Hepatology. Feb 2004;39(2):403–411.

    PubMed  Google Scholar 

  35. Petersen B, Shupe T. Location is everything: the liver stem cell niche. Hepatology. Jun 2008;47(6):1810–1812.

    PubMed  Google Scholar 

  36. Crosby HA, Kelly DA, Strain AJ. Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium. Gastroenterology. Feb 2001;120(2):534–544.

    CAS  PubMed  Google Scholar 

  37. Nagy P, Bisgaard HC, Thorgeirsson SS. Expression of hepatic transcription factors during liver development and oval cell differentiation. J Cell Biol. Jul 1994;126(1):223–233.

    CAS  PubMed  Google Scholar 

  38. Wang X, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci U S A. Sep 30 2003;100 Suppl 1:11881–11888.

    CAS  PubMed  Google Scholar 

  39. Theise ND, Saxena R, Portmann BC, et al. The canals of Hering and hepatic stem cells in humans. Hepatology. Dec 1999;30(6):1425–1433.

    CAS  PubMed  Google Scholar 

  40. Sell S. Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury. Hepatology. Feb 1998;27(2):317–331.

    CAS  PubMed  Google Scholar 

  41. Roskams T, Yang SQ, Koteish A, et al. Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. Am J Pathol. Oct 2003;163(4):1301–1311.

    CAS  PubMed  Google Scholar 

  42. Roskams TA, Libbrecht L, Desmet VJ. Progenitor cells in diseased human liver. Semin Liver Dis. Nov 2003;23(4):385–396.

    CAS  PubMed  Google Scholar 

  43. Lowes KN, Brennan BA, Yeoh GC, Olynyk JK. Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am J Pathol. Feb 1999;154(2):537–541.

    CAS  PubMed  Google Scholar 

  44. Mitaka T, Kojima T, Mizuguchi T, Mochizuki Y. Growth and maturation of small hepatocytes isolated from adult rat liver. Biochem Biophys Res Commun. Sep 14 1995;214(2):310–317.

    CAS  PubMed  Google Scholar 

  45. Sidler Pfandler MA, Hochli M, Inderbitzin D, Meier PJ, Stieger B. Small hepatocytes in culture develop polarized transporter expression and differentiation. J Cell Sci. Aug 15 2004;117(Pt 18):4077–4087.

    PubMed  Google Scholar 

  46. Chen Q, Kon J, Ooe H, Sasaki K, Mitaka T. Selective proliferation of rat hepatocyte progenitor cells in serum-free culture. Nat Protoc. 2007;2(5): 1197–1205.

    CAS  PubMed  Google Scholar 

  47. Oshima H, Kon J, Ooe H, Hirata K, Mitaka T. Functional expression of organic anion transporters in hepatic organoids reconstructed by rat small hepatocytes. J Cell Biochem. May 1 2008;104(1):68–81.

    CAS  PubMed  Google Scholar 

  48. Sicklick JK, Choi SS, Bustamante M, et al. Evidence for epithelial-mesenchymal transitions in adult liver cells. Am J Physiol Gastrointest Liver Physiol. Oct 2006;291(4):G575–583.

    CAS  PubMed  Google Scholar 

  49. Lim YS, Lee HC, Lee HS. Switch of cadherin expression from E- to N-type during the activation of rat hepatic stellate cells. Histochem Cell Biol. Feb 2007;127(2):149–160.

    CAS  PubMed  Google Scholar 

  50. Cassiman D, Roskams T. Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic stellate cell research. J Hepatol. Oct 2002;37(4): 527–535.

    PubMed  Google Scholar 

  51. Suskind DL, Muench MO. Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells. J Hepatol. Feb 2004;40(2):261–268.

    CAS  PubMed  Google Scholar 

  52. Yang L, Jung Y, Omenetti A, et al. Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers. Stem Cells. Aug 2008;26(8):2104–2113.

    CAS  PubMed  Google Scholar 

  53. Kordes C, Sawitza I, Muller-Marbach A, et al. CD133+ hepatic stellate cells are progenitor cells. Biochem Biophys Res Commun. Jan 12 2007;352(2):410–417.

    CAS  PubMed  Google Scholar 

  54. Sawitza I, Kordes C, Reister S, Haussinger D. The niche of stellate cells within rat liver. Hepatology. Nov 2009;50(5):1617–1624.

    CAS  PubMed  Google Scholar 

  55. Kordes C, Sawitza I, Haussinger D. Hepatic and pancreatic stellate cells in focus. Biol Chem. Oct 2009;390(10):1003–1012.

    CAS  PubMed  Google Scholar 

  56. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast: one function, multiple origins. Am J Pathol. Jun 2007;170(6):1807–1816.

    CAS  PubMed  Google Scholar 

  57. Parekkadan B, van Poll D, Megeed Z, et al. Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Biochem Biophys Res Commun. Nov 16 2007;363(2):247–252.

    CAS  PubMed  Google Scholar 

  58. Herrera MB, Bruno S, Buttiglieri S, et al. Isolation and characterization of a stem cell population from adult human liver. Stem Cells. Dec 2006;24(12):2840–2850.

    CAS  PubMed  Google Scholar 

  59. Kuwahara R, Kofman AV, Landis CS, Swenson ES, Barendswaard E, Theise ND. The hepatic stem cell niche: identification by label-retaining cell assay. Hepatology. Jun 2008;47(6):1994–2002.

    PubMed  Google Scholar 

  60. Brooling JT, Campbell JS, Mitchell C, Yeoh GC, Fausto N. Differential regulation of rodent hepatocyte and oval cell proliferation by interferon gamma. Hepatology. Apr 2005;41(4):906–915.

    CAS  PubMed  Google Scholar 

  61. Jakubowski A, Ambrose C, Parr M, et al. TWEAK induces liver progenitor cell proliferation. J Clin Invest. Sep 2005;115(9):2330–2340.

    CAS  PubMed  Google Scholar 

  62. Knight B, Matthews VB, Akhurst B, et al. Liver inflammation and cytokine production, but not acute phase protein synthesis, accompany the adult liver progenitor (oval) cell response to chronic liver injury. Immunol Cell Biol. Aug 2005;83(4):364–374.

    CAS  PubMed  Google Scholar 

  63. Lim R, Knight B, Patel K, McHutchison JG, Yeoh GC, Olynyk JK. Antiproliferative effects of interferon alpha on hepatic progenitor cells in vitro and in vivo. Hepatology. May 2006;43(5):1074–1083.

    CAS  PubMed  Google Scholar 

  64. Nguyen LN, Furuya MH, Wolfraim LA, et al. Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation. Hepatology. Jan 2007;45(1):31–41.

    CAS  PubMed  Google Scholar 

  65. Hatch HM, Zheng D, Jorgensen ML, Petersen BE. SDF-1alpha/CXCR4: a mechanism for hepatic oval cell activation and bone marrow stem cell recruitment to the injured liver of rats. Cloning Stem Cells. 2002;4(4):339–351.

    CAS  PubMed  Google Scholar 

  66. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. Apr 14 2005;434(7035):843–850.

    CAS  PubMed  Google Scholar 

  67. He TC, Sparks AB, Rago C, et al. Identification of c-MYC as a target of the APC pathway. Science. Sep 4 1998;281(5382):1509–1512.

    CAS  PubMed  Google Scholar 

  68. Hu M, Kurobe M, Jeong YJ, et al. Wnt/beta-catenin signaling in murine hepatic transit amplifying progenitor cells. Gastroenterology. Nov 2007;133(5):1579–1591.

    CAS  PubMed  Google Scholar 

  69. Apte U, Thompson MD, Cui S, Liu B, Cieply B, Monga SP. Wnt/beta-catenin signaling mediates oval cell response in rodents. Hepatology. Jan 2008;47(1):288–295.

    CAS  PubMed  Google Scholar 

  70. Sicklick JK, Li YX, Melhem A, et al. Hedgehog signaling maintains resident hepatic progenitors throughout life. Am J Physiol Gastrointest Liver Physiol. May 2006;290(5):G859–870.

    CAS  PubMed  Google Scholar 

  71. Mishra L, Banker T, Murray J, et al. Liver stem cells and hepatocellular carcinoma. Hepatology. Jan 2009;49(1):318–329.

    PubMed  Google Scholar 

  72. Tang Y, Kitisin K, Jogunoori W, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci U S A. Feb 19 2008;105(7):2445–2450.

    CAS  PubMed  Google Scholar 

  73. Scharenberg CW, Harkey MA, Torok-Storb B. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood. Jan 15 2002;99(2):507–512.

    CAS  PubMed  Google Scholar 

  74. Shafritz DA, Hadziyannis SJ. Molecular pathophysiology of persistent hepatitis B virus infection in relation to chronic liver disease and primary hepatocellular carcinoma. Monogr Pathol. 1987(28):136–152.

    Google Scholar 

  75. Wu PC, Lai VC, Fang JW, Gerber MA, Lai CL, Lau JY. Hepatocellular carcinoma expressing both hepatocellular and biliary markers also expresses cytokeratin 14, a marker of bipotential progenitor cells. J Hepatol. Nov 1999;31(5):965–966.

    CAS  PubMed  Google Scholar 

  76. Roskams T. Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene. Jun 26 2006;25(27):3818–3822.

    CAS  PubMed  Google Scholar 

  77. Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. Jul 2006;44(1):240–251.

    CAS  PubMed  Google Scholar 

  78. Mito M, Kusano M, Onishi T, Saito T, Ebata H. Hepatocellular transplantation—morphological study on hepatocytes transplanted into rat spleen. Gastroenterol Jpn. 1978;13(6):480–490.

    CAS  PubMed  Google Scholar 

  79. Raper SE, Wilson JM. Cell transplantation in liver-directed gene therapy. Cell Transplant. Sep-Oct 1993;2(5):381–400; discussion 407-310.

    CAS  PubMed  Google Scholar 

  80. Michel JL, Rabier D, Rambaud C, et al. [Intrasplenic transplantation of hepatocytes in spf-ash mice with congenital ornithine transcarbamylase deficiency]. Chirurgie. 1993;119(10):666–671.

    PubMed  Google Scholar 

  81. Rozga J, Holzman M, Moscioni AD, Fujioka H, Morsiani E, Demetriou AA. Repeated intraportal hepatocyte transplantation in analbuminemic rats. Cell Transplant. Mar-Apr 1995;4(2):237–243.

    CAS  PubMed  Google Scholar 

  82. Selden C, Calnan D, Morgan N, Wilcox H, Carr E, Hodgson HJ. Histidinemia in mice: a metabolic defect treated using a novel approach to hepatocellular transplantation. Hepatology. May 1995;21(5):1405–1412.

    CAS  PubMed  Google Scholar 

  83. Yoshida Y, Tokusashi Y, Lee GH, Ogawa K. Intrahepatic transplantation of normal hepatocytes prevents Wilson's disease in Long-Evans cinnamon rats. Gastroenterology. Dec 1996;111(6):1654–1660.

    CAS  PubMed  Google Scholar 

  84. Overturf K, al-Dhalimy M, Ou CN, Finegold M, Grompe M. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. Am J Pathol. Nov 1997;151(5):1273–1280.

    CAS  PubMed  Google Scholar 

  85. De Vree JM, Ottenhoff R, Bosma PJ, Smith AJ, Aten J, Oude Elferink RP. Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis. Gastroenterology. Dec 2000;119(6):1720–1730.

    PubMed  Google Scholar 

  86. Wiederkehr JC, Kondos GT, Pollak R. Hepatocyte transplantation for the low-density lipoprotein receptor-deficient state. A study in the Watanabe rabbit. Transplantation. Sep 1990;50(3):466–471.

    CAS  PubMed  Google Scholar 

  87. Kocken JM, Borel Rinkes IH, Bijma AM, et al. Correction of an inborn error of metabolism by intraportal hepatocyte transplantation in a dog model. Transplantation. Aug 15 1996;62(3):358–364.

    CAS  PubMed  Google Scholar 

  88. Sommer BG, Sutherland DE, Matas AJ, Simmons RL, Najarian JS. Hepatocellular transplantation for treatment of D-galactosamine-induced acute liver failure in rats. Transplant Proc. Mar 1979;11(1):578–584.

    CAS  PubMed  Google Scholar 

  89. Minato M, Houssin D, Demma I, et al. Transplantation of hepatocytes for treatment of surgically induced acute hepatic failure in the rat. Eur Surg Res. 1984;16(3):162–169.

    CAS  PubMed  Google Scholar 

  90. Demetriou AA, Reisner A, Sanchez J, Levenson SM, Moscioni AD, Chowdhury JR. Transplantation of microcarrier-attached hepatocytes into 90% partially hepatectomized rats. Hepatology. Sep-Oct 1988;8(5):1006–1009.

    CAS  PubMed  Google Scholar 

  91. Takeshita K, Ishibashi H, Suzuki M, Kodama M. Hepatocellular transplantation for metabolic support in experimental acute ischemic liver failure in rats. Cell Transplant. Jul-Aug 1993;2(4):319–324.

    CAS  PubMed  Google Scholar 

  92. Fox IJ, Chowdhury JR, Kaufman SS, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. May 14 1998;338(20):1422–1426.

    CAS  PubMed  Google Scholar 

  93. Muraca M, Gerunda G, Neri D, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet. Jan 26 2002;359(9303):317–318.

    PubMed  Google Scholar 

  94. Stephenne X, Najimi M, Sibille C, Nassogne MC, Smets F, Sokal EM. Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency. Gastroenterology. Apr 2006;130(4):1317–1323.

    PubMed  Google Scholar 

  95. Dhawan A, Mitry RR, Hughes RD, et al. Hepatocyte transplantation for inherited factor VII deficiency. Transplantation. Dec 27 2004;78(12):1812–1814.

    PubMed  Google Scholar 

  96. Horslen SP, McCowan TC, Goertzen TC, et al. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics. Jun 2003;111(6 Pt 1):1262–1267.

    PubMed  Google Scholar 

  97. Habibullah CM, Syed IH, Qamar A, Taher-Uz Z. Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation. Oct 27 1994;58(8):951–952.

    CAS  PubMed  Google Scholar 

  98. Strom SC, Fisher RA, Rubinstein WS, et al. Transplantation of human hepatocytes. Transplant Proc. Jun 1997;29(4):2103–2106.

    CAS  PubMed  Google Scholar 

  99. Strom SC, Chowdhury JR, Fox IJ. Hepatocyte transplantation for the treatment of human disease. Semin Liver Dis. 1999;19(1):39–48.

    CAS  PubMed  Google Scholar 

  100. Bilir BM, Guinette D, Karrer F, et al. Hepatocyte transplantation in acute liver failure. Liver Transpl. Jan 2000;6(1):32–40.

    CAS  PubMed  Google Scholar 

  101. Fisher RA, Bu D, Thompson M, et al. Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion. Transplantation. Jan 27 2000;69(2):303–307.

    CAS  PubMed  Google Scholar 

  102. Meyburg J, Hoerster F, Weitz J, Hoffmann GF, Schmidt J. Use of the middle colic vein for liver cell transplantation in infants and small children. Transplant Proc. May 2008;40(4):936–937.

    CAS  PubMed  Google Scholar 

  103. Fausto N, Riehle KJ. Mechanisms of liver regeneration and their clinical implications. J Hepatobiliary Pancreat Surg. 2005;12(3):181–189.

    PubMed  Google Scholar 

  104. Teratani T, Yamamoto H, Aoyagi K, et al. Direct hepatic fate specification from mouse embryonic stem cells. Hepatology. Apr 2005;41(4):836–846.

    CAS  PubMed  Google Scholar 

  105. Ishii T, Yasuchika K, Machimoto T, et al. Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage. Stem Cells. Dec 2007;25(12):3252–3260.

    CAS  PubMed  Google Scholar 

  106. Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood. Nov 15 2003;102(10):3483–3493.

    CAS  PubMed  Google Scholar 

  107. Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med. Nov 2000;6(11): 1229–1234.

    CAS  PubMed  Google Scholar 

  108. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science. May 14 1999;284(5417):1168–1170.

    CAS  PubMed  Google Scholar 

  109. Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. Jan 2000;31(1):235–240.

    CAS  PubMed  Google Scholar 

  110. Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology. Jul 2000;32(1):11–16.

    CAS  PubMed  Google Scholar 

  111. Fujino H, Hiramatsu H, Tsuchiya A, et al. Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/gamma(c)null mice through cell fusion. Faseb J. Nov 2007;21(13):3499–3510.

    CAS  PubMed  Google Scholar 

  112. Quintana-Bustamante O, Alvarez-Barrientos A, Kofman AV, et al. Hematopoietic mobilization in mice increases the presence of bone marrow-derived hepatocytes via in vivo cell fusion. Hepatology. Jan 2006;43(1):108–116.

    PubMed  Google Scholar 

  113. am Esch JS, 2nd, Knoefel WT, Klein M, et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells. Apr 2005;23(4):463–470.

    Google Scholar 

  114. Cantz T, Sharma AD, Jochheim-Richter A, et al. Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration. Cell Transplant. 2004;13(6):659–666.

    PubMed  Google Scholar 

  115. Kanazawa Y, Verma IM. Little evidence of bone marrow-derived hepatocytes in the replacement of injured liver. Proc Natl Acad Sci U S A. Sep 30 2003;100 Suppl 1:11850–11853.

    CAS  PubMed  Google Scholar 

  116. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. Sep 27 2002;297(5590):2256–2259.

    CAS  PubMed  Google Scholar 

  117. Schmelzer E, Zhang L, Bruce A, et al. Human hepatic stem cells from fetal and postnatal donors. J Exp Med. Aug 6 2007;204(8):1973–1987.

    CAS  PubMed  Google Scholar 

  118. Yamashita T, Forgues M, Wang W, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. Mar 1 2008;68(5):1451–1461.

    CAS  PubMed  Google Scholar 

  119. Yang ZF, Ngai P, Ho DW, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. Mar 2008;47(3):919–928.

    CAS  PubMed  Google Scholar 

  120. Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. Feb 2008;13(2):153–166.

    CAS  PubMed  Google Scholar 

  121. Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. Jun 2007;132(7):2542–2556.

    CAS  PubMed  Google Scholar 

  122. Kitisin K, Ganesan N, Tang Y, et al. Disruption of transforming growth factor-beta signaling through beta-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation. Oncogene. Nov 1 2007;26(50):7103–7110.

    CAS  PubMed  Google Scholar 

  123. Kim H, Park C, Han KH, et al. Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. J Hepatol. Feb 2004;40(2):298–304.

    CAS  PubMed  Google Scholar 

  124. Seki T. Microenvironmental elements supporting adult hippocampal neurogenesis. Anat Sci Int. Jun 2003;78(2):69–78.

    PubMed  Google Scholar 

  125. Yang W, Yan HX, Chen L, et al. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res. Jun 1 2008;68(11):4287–4295.

    CAS  PubMed  Google Scholar 

  126. Yin S, Li J, Hu C, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer. Apr 1 2007;120(7):1444–1450.

    CAS  PubMed  Google Scholar 

  127. Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. Dec 29 2006;351(4):820–824.

    CAS  PubMed  Google Scholar 

  128. Roskams T, De Vos R, Van Eyken P, Myazaki H, Van Damme B, Desmet V. Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man. J Hepatol. Sep 1998;29(3):455–463.

    CAS  PubMed  Google Scholar 

  129. Xiao JC, Ruck P, Adam A, Wang TX, Kaiserling E. Small epithelial cells in human liver cirrhosis exhibit features of hepatic stem-like cells: immunohistochemical, electron microscopic and immunoelectron microscopic findings. Histopathology. Feb 2003;42(2):141–149.

    PubMed  Google Scholar 

  130. Kawai HF, Kaneko S, Honda M, Shirota Y, Kobayashi K. alpha-fetoprotein-producing hepatoma cell lines share common expression profiles of genes in various categories demonstrated by cDNA microarray analysis. Hepatology. Mar 2001;33(3):676–691.

    CAS  PubMed  Google Scholar 

  131. Blakolmer K, Jaskiewicz K, Dunsford HA, Robson SC. Hematopoietic stem cell markers are expressed by ductal plate and bile duct cells in developing human liver. Hepatology. Jun 1995;21(6):1510–1516.

    CAS  PubMed  Google Scholar 

  132. Haque S, Haruna Y, Saito K, et al. Identification of bipotential progenitor cells in human liver regeneration. Lab Invest. Nov 1996;75(5):699–705.

    CAS  PubMed  Google Scholar 

  133. Stamp L, Crosby HA, Hawes SM, Strain AJ, Pera MF. A novel cell-surface marker found on human embryonic hepatoblasts and a subpopulation of hepatic biliary epithelial cells. Stem Cells. 2005;23(1):103–112.

    CAS  PubMed  Google Scholar 

  134. Yang Y, Zheng J, Zhou X, et al. Potential treatment of liver-related disorders with in vitro expanded human liver precursors. Differentiation. Dec 2007;75(10):928–938.

    CAS  PubMed  Google Scholar 

  135. Terada T, Nakanuma Y, Sirica AE. Immunohistochemical demonstration of MET overexpression in human intrahepatic cholangiocarcinoma and in hepatolithiasis. Hum Pathol. Feb 1998;29(2):175–180.

    CAS  PubMed  Google Scholar 

  136. Fabris L, Strazzabosco M, Crosby HA, et al. Characterization and isolation of ductular cells coexpressing neural cell adhesion molecule and Bcl-2 from primary cholangiopathies and ductal plate malformations. Am J Pathol. May 2000;156(5):1599–1612.

    CAS  PubMed  Google Scholar 

  137. Lemmer ER, Shepard EG, Blakolmer K, Kirsch RE, Robson SC. Isolation from human fetal liver of cells co-expressing CD34 haematopoietic stem cell and CAM 5.2 pancytokeratin markers. J Hepatol. Sep 1998;29(3):450–454.

    CAS  PubMed  Google Scholar 

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He, A.R., Thenappan, A., Abdul Khalek, F.J., Mishra, L. (2011). Stem Cells and Chronic Liver Failure: Potential New Therapeutics. In: Ginès, P., Kamath, P., Arroyo, V. (eds) Chronic Liver Failure. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60761-866-9_6

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