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Mesenchymal Stem Cells for Liver Regeneration

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Stem Cells & Regenerative Medicine

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

The liver is an extraordinary organ that retains its regenerative power throughout life. The precise molecular mechanisms regulating liver regeneration are unknown, but a number of cell types have been postulated to be involved in the process, including (1) resident liver stem cells, (2) differentiated hepatocytes, and (3) extrahepatic stem cells. This chapter will discuss liver regeneration from the context of extrahepatic stem cells. Recent research findings have challenged the dogma of limited lineage commitment potency of somatic stem cells. This chapter reviews the hepatic lineage plasticity of mesenchymal stem cells in vitro and in. In addition, it discusses developments in the application of mesenchymal stem cells for the treatment of liver diseases in preclinical and clinical studies, as well as in possible signaling pathways and mechanisms, including microRNAs, which are involved in the regulatory control of hepatic fate specification.

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References

  1. Sirica, A.E., Mathis, G.A., Sano, N., et al. (1990) Isolation, culture, and transplantation of intrahepatic biliary epithelial cells and oval cells. Pathobiology. 58, 44–64.

    Article  PubMed  CAS  Google Scholar 

  2. Ruch, R.J. and Trosko, J.E. (1999) The role of oval cells and gap junctional intercellular communication in hepatocarcinogenesis. Anticancer Res. 19, 4831–4838.

    PubMed  CAS  Google Scholar 

  3. Fausto, N. and Campbell, J.S. (2003) The role of hepatocytes and oval cells in liver regeneration and repopulation. Mech. Dev. 120, 117–130.

    Article  PubMed  CAS  Google Scholar 

  4. Newsome, P.N., Hussain, M.A. and Theise, N.D. (2004) Hepatic oval cells: helping redefine a paradigm in stem cell biology. Curr. Top. Dev. Biol. 61, 1–28.

    Article  PubMed  CAS  Google Scholar 

  5. Petersen, B.E., Bowen, W.C., Patrene, K.D., et al. (1999) Bone marrow as a potential source of hepatic oval cells. Science. 284, 1168–1170.

    Article  PubMed  CAS  Google Scholar 

  6. Theise, N. D., Badve, S., Saxena, R., et al., (2000) Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 31, 235–240.

    Article  PubMed  CAS  Google Scholar 

  7. Theise, N.D., Nimmakayalu, M., Gardner, R., et al. (2000) Liver from bone marrow in humans. Hepatology. 32, 11–16.

    Article  PubMed  CAS  Google Scholar 

  8. Alison, M.R., Poulsom, R., Jeffery, R., et al. (2000) Hepatocytes from non-hepatic adult stem cells. Nature. 406, 257.

    Article  PubMed  CAS  Google Scholar 

  9. Fujio, K., Evarts, R.P., Hu, Z., et al. (1994) Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab. Invest. 70, 511–516.

    PubMed  CAS  Google Scholar 

  10. Petersen, B.E., Goff, J.P., Greenberger, J.S., et al. (1998) Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology. 27, 433–445.

    Article  PubMed  CAS  Google Scholar 

  11. Petersen, B.E., Grossbard, B., Hatch, H., et al. (2003) Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers. Hepatology. 37, 632–640.

    Article  PubMed  Google Scholar 

  12. Körbling, M., Katz, R.L., Khanna, A., et al. (2002) Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N. Engl. J. Med. 346, 738–46.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Krause, D.S., Theise, N.D., Collector, M.I., et al. (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 105, 369–377.

    Article  PubMed  CAS  Google Scholar 

  15. Terada, N., Hamazaki, T., Oka, M., et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 416, 542–545.

    Article  PubMed  CAS  Google Scholar 

  16. Ying, Q.L., Nichols, J., Evans, E.P., et al. (2002) Changing potency by spontaneous fusion. Nature. 416, 545–548.

    Article  PubMed  CAS  Google Scholar 

  17. Wang, X., Willenbring, H., Akkari, Y., et al. (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 422, 897–901.

    Article  PubMed  CAS  Google Scholar 

  18. Vassilopoulos, G., Wang, P.R. and Russell, D.W. (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature. 422, 901–904.

    Article  PubMed  CAS  Google Scholar 

  19. Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J.M., et al. (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 425, 968–973.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Camargo, F.D., Finegold, M. and Goodell, M.A. (2004) Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J. Clin. Invest. 11, 1266–1270.

    Google Scholar 

  22. Oh, S.H., Miyazaki, M., Kouchi, H., et al. (2000) Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro. Biochem. Biophys. Res. Commun. 279, 500–504.

    Article  PubMed  CAS  Google Scholar 

  23. Miyazaki, M., Akiyama, I., Sakaguchi, M., et al. (2002) Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Biochem. Biophys. Res. Commun. 298, 24–30.

    Article  PubMed  CAS  Google Scholar 

  24. Schwartz, R.E., Reyes, M., Koodie, L., et al. (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Invest. 109, 1291–1302.

    PubMed  CAS  Google Scholar 

  25. Jiang, Y., Jahagirdar, B.N., Reinhardt, R.L., et al. (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 418, 41–49.

    Article  PubMed  CAS  Google Scholar 

  26. Deans, R.J., and Moseley, A.B. (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp. Hematol. 28, 875–884.

    Article  PubMed  CAS  Google Scholar 

  27. Barry, F.P., and Murphy, J.M. (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int. J. Biochem. Cell Biol. 36, 568–584.

    Article  PubMed  CAS  Google Scholar 

  28. Kuo, T.K., Ho, J.H., and Lee, O.K. (2009) Mesenchymal stem cell therapy for non- musculoskeletal diseases: emerging applications. Cell Transplant. 18(9):1013–1028.

    Article  PubMed  Google Scholar 

  29. Petrakova, K.V., Tolmacheva, A.A., Friedenstein, A.J. (1963) Bone formation occurring in bone marrow transplantation in diffusion chambers. Bull. Exp. Biol. Med. 56, 87–91.

    Article  CAS  Google Scholar 

  30. Friedenstein, A.J., Chailakhyan, R.K. and Lalykina, K.S. (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 3, 393–403.

    PubMed  CAS  Google Scholar 

  31. Beresford, J.N., Bennet, J.H., Devlin, C., et al. (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J. Cell Sci. 102, 341–351.

    PubMed  CAS  Google Scholar 

  32. Caplan, A.I. (1991) Mesenchymal stem cells. J. Orthop. Res. 9, 641–650.

    Article  PubMed  CAS  Google Scholar 

  33. Cheng, S.L., Yang, J.W., Rifas, L., et al. (1994) Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology. 134, 277–286.

    Article  PubMed  CAS  Google Scholar 

  34. Clark, B.R. and Keating, A. (1995) Biology of bone marrow stroma. Ann. N. Y. Acad. Sci. 770, 70–78.

    Article  PubMed  CAS  Google Scholar 

  35. Friedenstein, A.J., Chailakhyan, R.K. and Gerasimov, U.V. (1987) Bone marrow Osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet. 20, 263–272.

    PubMed  CAS  Google Scholar 

  36. Keating, A., Horsfall, W., Hawley, R.G., et al. (1990) Effect of different promoters on expression of genes introduced into hematopoietic and marrow stromal cells by electroporation. Exp. Hematol. 18, 99–102.

    PubMed  CAS  Google Scholar 

  37. Rickard, D.J., Sullivan, T.A., Shenker, B.J., et al. (1994) Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. Dev. Biol. 161, 218–228.

    Article  PubMed  Google Scholar 

  38. Umezawa, A., Maruyama, T., Segawa, K., et al. (1992) Multipotent marrow stromal cell line is able to induce hematopoiesis in vivo. J. Cell. Physiol. 151, 197–205.

    Article  PubMed  CAS  Google Scholar 

  39. Wakitani, S., Saito, T., Caplan, A.I. (1995) Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 18, 1417–1426.

    Article  PubMed  CAS  Google Scholar 

  40. Pittenger, M.F., Mackay, A.M., Beck, S.C., et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science. 284, 143–147.

    Article  PubMed  CAS  Google Scholar 

  41. Muraglia, A., Cancedda, R. and Quarto, R. (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J. Cell Sci. 117, 1161–1166.

    Google Scholar 

  42. da Silva Meirelles, L., Chagastelles, P.C. and Nardi, N.B. (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci. 119, 2204–2213.

    Article  PubMed  CAS  Google Scholar 

  43. De Bari, C., Dell-Accio, F., Tylzanowski, P., et al. (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 44, 1928–1942.

    Article  PubMed  CAS  Google Scholar 

  44. Erices, A.A., Allers, C.I., Conget, P.A., et al. (2003) Human cord blood-derived mesenchymal stem cells home and survive in the marrow of immunodeficient mice after systemic infusion. Cell Transplant. 12, 555–561.

    PubMed  Google Scholar 

  45. Fickert, S., Fiedler, J., Brenner, R.E. (2003) Identification, quantification and isolation of mesenchymal progenitor cells from osteoarthritic synovium by fluorescence automated cell sorting. Osteoarthritis Cartilage. 11, 790–800.

    Article  PubMed  CAS  Google Scholar 

  46. Fukuchi, Y., Nakajima, H., Sugiyama, D., et al. (2004) Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells. 22, 649–658.

    Article  PubMed  CAS  Google Scholar 

  47. In’t Anker, P.S., Scherjon, S.A., Kleijburg-van Keur, C., et al. (2003) Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 102, 1548–1549

    Article  Google Scholar 

  48. Lee, O.K., Kuo, T.K., Chen, W.M., et al. (2004) Isolation and characterization of mesenchymal stem cells from umbilical cord blood. Blood. 103, 1669–1675.

    Article  PubMed  CAS  Google Scholar 

  49. Lucas, P.A., Calcutt, A.F., Southerland, S.S., et al. (1995) A population of cells resident within embryonic and newborn rat skeletal muscle is capable of differentiating into multiple mesodermal phenotypes. Wound Repair Regen. 3, 449–460.

    Article  PubMed  CAS  Google Scholar 

  50. Sakaguchi, Y., Sekiya, I., Yagishita, K., et al. (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 52, 2521–2529.

    Article  PubMed  Google Scholar 

  51. Shih, D.T., Lee, D.C., Chen, S.C., et al. (2005) Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue. Stem Cells. 23, 1012–1020.

    Article  PubMed  CAS  Google Scholar 

  52. Sottile, V., Halleux, C., Bassilana, F., et al. (2002) Stem cell characteristics of human trabecular bone-derived cells. Bone. 30, 699–704.

    Article  PubMed  CAS  Google Scholar 

  53. Tondreau, T., Meuleman, N., Delforge, A., et al. (2005) Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells. 23, 1105–1112.

    Article  PubMed  CAS  Google Scholar 

  54. Tsai, M.S., Lee, J.L., Chang, Y.J., et al. (2004) Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum. Reprod. 19, 1450–1456.

    Article  PubMed  Google Scholar 

  55. Tuli, R., Tuli, S., Nandi, S., et al. (2003) Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone. Stem Cells. 21, 681–693.

    Article  PubMed  CAS  Google Scholar 

  56. Villaron, E.M., Almeida, J., Lopez-Holgado, N., et al. (2004) Mesenchymal stem cells are present in peripheral blood and can engraft allogeneic hematopoietic stem cell transplantation. Haematologica. 89, 1421–1427.

    PubMed  Google Scholar 

  57. Wang, H.S., Hung, S.C., Peng, S.T., et al. (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 22, 1330–1337.

    Article  PubMed  Google Scholar 

  58. Wulf, G.G., Viereck, V., Hemmerlein, B., et al. (2004) Mesengenic progenitor cells derived from human placenta. Tissue Eng. 10, 1136–1147.

    PubMed  CAS  Google Scholar 

  59. Yañez, R., Lamana, M.L., García-Castro, J., et al. (2006) Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells. 24, 2582–2591.

    Article  PubMed  CAS  Google Scholar 

  60. Young, H.E., Ceballos, E.M., Smith, J.C., et al. (1993) Pluripotent mesenchymal stem cells reside within avian connective tissue matrices. In Vitro Cell. Dev. Biol. Anim. 29A, 723–736.

    Article  PubMed  CAS  Google Scholar 

  61. Zuk, P.A., Zhu, M., Mizuno, H., et al. (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211–228.

    Article  PubMed  CAS  Google Scholar 

  62. Zaret, K.S. (1996) Molecular genetics of early liver development. Annu. Rev. Physiol. 58, 231–251.

    Article  PubMed  CAS  Google Scholar 

  63. Zaret, K.S. (2000) Liver specification and early morphogenesis. Mech. Dev. 92, 83–88.

    Article  PubMed  CAS  Google Scholar 

  64. Schmidt, C., Bladt, F., Goedecke, S., et al. (1995) Scatter factor/hepatocyte growth factor is essential for liver development. Nature. 373, 699–702.

    Article  PubMed  CAS  Google Scholar 

  65. Bladt, F., Riethmacher, D., Isenmann, S., et al. (1995) Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature. 376, 768–771.

    Article  PubMed  CAS  Google Scholar 

  66. Hilberg, F., Aguzzi, A., Howells, N., et al. (1997) c-jun is essential for normal mouse development and hepatogenesis. Nature. 365, 179–181.

    Article  Google Scholar 

  67. Hentsch, B., Lyons, I., Li, R., et al. (1996) Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut. Genes Dev. 10, 70–79.

    Article  PubMed  CAS  Google Scholar 

  68. Beg, A.A., Sha, W.C., Bronson, R.T., et al. (1998) Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. EMBO J. 17, 2846–2854.

    Article  Google Scholar 

  69. Giroux, S. and Charron, J. (1998) Defective development of the embryonic liver in N-myc-deficient mice. Dev. Biol. 195, 16–28.

    Article  PubMed  CAS  Google Scholar 

  70. Nishina, H., Vaz, C., Billia, P., et al. (1999) Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4. Development. 126, 505–516.

    PubMed  CAS  Google Scholar 

  71. Motoyama, J., Kitajima, K., Kojima, M., et al. (1997) Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice. Mech. Dev. 66, 27–37.

    Article  PubMed  CAS  Google Scholar 

  72. Kasper, G., Dankert, N., Tuischer, J., et al. (2007) Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells. 25, 903–910.

    Article  PubMed  CAS  Google Scholar 

  73. Rider, D.A., Dombrowski, C., Sawyer, A.A., et al. (2008) Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells. Stem Cells. 26, 1598–1608.

    Article  PubMed  CAS  Google Scholar 

  74. Neuss, S., Becher, E., Wöltje, M., et al. (2004) Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells. 22, 405–414.

    Article  PubMed  CAS  Google Scholar 

  75. Forte, G., Minieri, M., Cossa, P., et al. (2006) Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells. 24, 23–33.

    Article  PubMed  CAS  Google Scholar 

  76. Son, B.R., Marquez-Curtis, L.A., Kucia, M., et al. (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells. 24, 1254–1264.

    Article  PubMed  CAS  Google Scholar 

  77. Ciruna, B.G., Schwartz, L., Harpal, K., et al. (1997) Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak. Development. 124, 2829–2841.

    PubMed  CAS  Google Scholar 

  78. Lee, K.D., Kuo, T.K., Chung, Y.F., et al. (2004) In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 40, 1275–1284.

    Article  PubMed  CAS  Google Scholar 

  79. Trusolino, L., and Comoglio, P.M. (2002) Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev. Cancer. 2, 289–300.

    Article  PubMed  CAS  Google Scholar 

  80. Snykers, S., Vanhaecke, T., Papeleu, P., et al. (2006) Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicol. Sci. 94, 330–341.

    Article  PubMed  CAS  Google Scholar 

  81. Banas, A., Teratani, T., Yamamoto, Y., et al. (2007) Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 46, 219–228.

    Article  PubMed  CAS  Google Scholar 

  82. Sgodda, M., Aurich, H., Kleist, S., et al. (2007) Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp. Cell Res. 313, 2875–2886.

    Article  PubMed  CAS  Google Scholar 

  83. Yoshida, Y., Shimomura, T., Sakabe, T., et al. (2007) A role of Wnt/beta-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G1089–1098.

    Article  PubMed  CAS  Google Scholar 

  84. Banas, A., Teratani, T., Yamamoto, Y., et al. (2009) Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J. Gastroenterol. Hepatol. 24, 70–77.

    Article  PubMed  CAS  Google Scholar 

  85. Kinoshita, T., Sekiguchi, T., Xu, M.J., et al. (1999) Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis. Proc. Natl. Acad. Sci. USA. 96, 7265–7270.

    Article  PubMed  CAS  Google Scholar 

  86. Kamiya, A., Kinoshita, T., Ito, Y., et al. (1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J. 18, 2127–2136.

    Article  PubMed  CAS  Google Scholar 

  87. Sakai, Y., Jiang, J., Kojima, N., et al. (2002) Enhanced in vitro maturation of fetal mouse liver cells with oncostatin M, nicotinamide, and dimethyl sulfoxide. Cell Transplant. 11, 435–441.

    PubMed  CAS  Google Scholar 

  88. Kamiya, A., Kinoshita, T. and Miyajima, A. (2001) Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways. FEBS Lett. 492, 90–94.

    Article  PubMed  CAS  Google Scholar 

  89. Okaya, A., Kitanaka, J., Kitanaka, N., et al. (2005) Oncostatin M inhibits proliferation of rat oval cells, OC15–5, inducing differentiation into hepatocytes. Am. J. Pathol. 166, 709–719.

    Article  PubMed  CAS  Google Scholar 

  90. Matsui, T., Kinoshita, T., Hirano, T., et al. (2002) STAT3 down-regulates the expression of cyclin D during liver development. J. Biol. Chem. 277, 36167–36173.

    Article  PubMed  CAS  Google Scholar 

  91. Ong, S.Y., Dai, H. and Leong, K.W. (2006) Hepatic differentiation potential of commercially available human mesenchymal stem cells. Tissue Eng. 12, 3477–3485.

    Article  PubMed  CAS  Google Scholar 

  92. Lysy, P.A., Campard, D., Smets, F., et al. (2008) Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells. Cell Prolif. 41, 36–58.

    Article  PubMed  CAS  Google Scholar 

  93. Stock, P., Staege, M.S., Müller, L.P., et al. (2008) Hepatocytes derived from adult stem cells. Transplant Proc. 40, 620–623.

    Article  PubMed  CAS  Google Scholar 

  94. Snykers, S., Vanhaecke, T., De Becker, A., et al. (2007) Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow. BMC Dev. Biol. 7, 24.

    Article  PubMed  CAS  Google Scholar 

  95. Lysy, P.A., Smets, F., Najimi, M., et al. (2008) Leukemia inhibitory factor contributes to hepatocyte-like differentiation of human bone marrow mesenchymal stem cells. Differentiation. 76, 1057–1067.

    Article  PubMed  CAS  Google Scholar 

  96. Henkens, T., Papeleu, P., Elaut, G., et al. (2007) Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes. Toxico.l Appl. Pharmacol. 218, 64–71.

    Article  CAS  Google Scholar 

  97. Schoeberlein, A., Holzgreve, W., Dudler, L., et al. (2005) Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses. Am. J. Obstet. Gynecol. 192, 1044–1052.

    Article  PubMed  CAS  Google Scholar 

  98. Chou, S.H., Kuo, T.K., Liu, M., et al. (2006) In utero transplantation of human bone marrow-derived multipotent mesenchymal stem cells in mice. J. Orthop. Res. 24, 301–312.

    Article  PubMed  Google Scholar 

  99. Sato, Y., Araki, H., Kato, J., et al. (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 106, 756–763.

    Article  PubMed  CAS  Google Scholar 

  100. Aurich, I., Mueller, L.P., Aurich, H., et al. (2007) Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 56, 405–415.

    Article  PubMed  CAS  Google Scholar 

  101. Chamberlain, J., Yamagami, T., Colletti, E., et al. (2007) Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep. Hepatology. 46, 1935–1945.

    Article  PubMed  CAS  Google Scholar 

  102. Samuel, D. (2002) Treatment of patients with hepatic failure. J. Gastroenterol. Hepatol. S3, S274–S279.

    Article  Google Scholar 

  103. Fox, I.J. and Roy-Chowdhury, J. (2004) Hepatocyte transplantation. J. Hepatol. 40, 878–886.

    Article  PubMed  CAS  Google Scholar 

  104. Lloyd, T.D., Orr, S., Skett, P., et al. (2003) Cryopreservation of hepatocytes: a review of current methods for banking. Cell Tissue Bank. 4, 3–15.

    Article  PubMed  CAS  Google Scholar 

  105. Gupta, S., Rajvanshi, P., Sokhi, R., et al. (1999) Entry and integration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium. Hepatology. 29, 509–519.

    Article  PubMed  CAS  Google Scholar 

  106. Gupta, S., and Chowdhury, J.R. (2002) Therapeutic potential of hepatocyte transplantation. Semin. Cell Dev. Biol. 13, 439–446.

    Article  PubMed  Google Scholar 

  107. Rajvanshi, P., Kerr, A., Bhargava, K.K., et al. (1996) Efficacy and safety of repeated hepatocyte transplantation for significant liver repopulation in rodents. Gastroenterology. 111, 1092–1102.

    Article  PubMed  CAS  Google Scholar 

  108. Rojkind, M., Gatmaitan, Z., Mackensen, S., et al. (1980) Connective tissue biomatrix: its isolation and utilization for long-term cultures of normal rat hepatocytes. J. Cell Biol. 87, 255–263.

    Article  PubMed  CAS  Google Scholar 

  109. Clement, B., Guguen-Guillouzo, C., Campion, J.P., et al. (1984) Long-term co-cultures of adult human hepatocytes with rat liver epithelial cells: modulation of albumin secretion and accumulation of extracellular material. Hepatology. 4, 373–380.

    Article  PubMed  CAS  Google Scholar 

  110. Tong, J.Z., Sarrazin, S., Cassio, D., et al. (1994) Application of spheroid culture to human hepatocytes and maintenance of their differentiation. Biol Cell. 81, 77–81.

    Article  PubMed  CAS  Google Scholar 

  111. Hino, H., Tateno, C., Sato, H., et al. (1999) A long-term culture of human hepatocytes which show a high growth potential and express their differentiated phenotypes. Biochem. Biophys. Res. Commun. 256, 184–191.

    Article  PubMed  CAS  Google Scholar 

  112. Katsura, N., Ikai, I., Mitaka, T., et al. (2002) Long-term culture of primary human hepatocytes with preservation of proliferative capacity and differentiated functions. J Surg Res. 106, 115–123.

    Article  PubMed  CAS  Google Scholar 

  113. Keeffe, E.B. (2001) Liver transplantation: current status and novel approaches to liver replacement. Gastroenterology. 120, 749–762.

    Article  PubMed  CAS  Google Scholar 

  114. Kuo, T.K., Hung, S.P., Chuang, C.H., et al. (2008) Stem cell therapy for liver disease: para meters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology. 134, 2111–2121.

    Article  PubMed  Google Scholar 

  115. Parekkadan, B., van Poll, D., Suganuma, K., et al. (2007) Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS ONE. 2, e941.

    Article  PubMed  CAS  Google Scholar 

  116. Yan, Y., Xu, W., Qian, H., et al. (2009) Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo. Liver Int. 29, 356–365.

    Article  PubMed  CAS  Google Scholar 

  117. Friedman, S.L. (2008) Mechanisms of hepatic fibrogenesis. Gastroenterology. 134, 1655–1669.

    Article  PubMed  CAS  Google Scholar 

  118. Zhao, D.C., Lei, J.X., Chen, R., et al. (2005) Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J. Gastroenterol. 11, 3431–3440.

    PubMed  Google Scholar 

  119. Abdel Aziz, M.T., Atta, H.M., Mahfouz, S., et al. (2007) Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin. Biochem. 40, 893–899.

    Article  PubMed  CAS  Google Scholar 

  120. Tsai, P.C., Fu, T.W., Chen, Y.M., et al. (2009) The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis. Liver Transpl. 15, 484–495.

    Article  PubMed  Google Scholar 

  121. Oyagi, S., Hirose, M., Kojima, M., et al. (2006) Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J. Hepatol. 44, 742–748.

    Article  PubMed  CAS  Google Scholar 

  122. Jung, K.H., Shin, H.P., Lee, S., et al. (2009) Effect of human umbilical cord blood-derived mesenchymal stem cells in a cirrhotic rat model. Liver Int. 29(6), 898–909.

    Article  PubMed  CAS  Google Scholar 

  123. Carvalho, A.B., Quintanilha, L.F., Dias, J.V., et al. (2008) Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury. Stem Cells. 26, 1307–1314.

    Article  PubMed  CAS  Google Scholar 

  124. Terai, S., Ishikawa, T., Omori, K., et al. (2006) Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 24, 2292–2298.

    Article  PubMed  CAS  Google Scholar 

  125. Mohamadnejad, M., Namiri, M., Bagheri, M., et al. (2007) Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J. Gastroenterol. 13, 3359–3363.

    PubMed  CAS  Google Scholar 

  126. Mohamadnejad, M., Alimoghaddam, K., Mohyeddin-Bonab, M., et al. (2007) Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch. Iran Med. 10, 459–466.

    PubMed  CAS  Google Scholar 

  127. Kharaziha, P., Hellström, P.M., Noorinayer, B., et al. (2009) Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur. J. Gastroenterol. Hepatol. 21(10), 1199–1205.

    Article  PubMed  CAS  Google Scholar 

  128. McLin, V.A., Rankin, S.A. and Zorn, A.M. (2007) Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development. 134, 2207–2217.

    Article  PubMed  CAS  Google Scholar 

  129. Gualdi, R., Bossard, P., Zheng, M., et al. (1996) Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev. 10, 1670–1682.

    Article  PubMed  CAS  Google Scholar 

  130. Wandzioch, E. and Zaret, K.S. (2009) Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science. 324, 1707–1710.

    Article  PubMed  CAS  Google Scholar 

  131. Ke, Z., Zhou, F., Wang, L., et al. (2008) Down-regulation of Wnt signaling could promote bone marrow-derived mesenchymal stem cells to differentiate into hepatocytes. Biochem. Biophys. Res. Commun. 367, 342–348.

    Article  PubMed  CAS  Google Scholar 

  132. Yamamoto, Y., Banas, A., Murata, S., et al. (2008) A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells. FEBS J. 275, 1260–1273.

    Article  PubMed  CAS  Google Scholar 

  133. Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75, 843–854.

    Article  PubMed  CAS  Google Scholar 

  134. Wightman, B., Ha, I., and Ruvkun, G. (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 75, 855–862.

    Article  PubMed  CAS  Google Scholar 

  135. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., et al. (2001) Identification of novel genes coding for small expressed RNAs. Science. 294, 853–858.

    Article  PubMed  CAS  Google Scholar 

  136. Lau, N.C., Lim, L.P., Weinstein, E.G., et al. (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. science. 294, 858–862.

    Google Scholar 

  137. Griffiths-Jones, S., Saini, H.K., Dongen, S.V., et al. (2007) miRBase: tools for microRNA genomics. Nucleic Acids Res. 360, D154–D158.

    Article  CAS  Google Scholar 

  138. Bentwich, I., Avniel, A., Karov, Y., et al. (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 37, 766–770.

    Article  PubMed  CAS  Google Scholar 

  139. Berezikov, E., Guryev, V., van de Belt, J., et al. (2005) Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 120, 21–24.

    Article  PubMed  CAS  Google Scholar 

  140. Calin, G.A. and Croce, C.M. (2006) MicroRNA signatures in human cancers. Nat. Rev. Cancer. 6, 857–66.

    Article  PubMed  CAS  Google Scholar 

  141. Lim, L.P., Glasner, M.E., Yekta, S., et al. (2003) Vertebrate microRNA genes. Science. 299, 1540.

    Article  PubMed  CAS  Google Scholar 

  142. Kim, V.N. (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat. Rev. Mol. Cell Biol. 6, 376–385.

    Article  PubMed  CAS  Google Scholar 

  143. Kim, V.N. (2005) Small RNAs: classification, biogenesis, and function. Mol. Cells. 19, 1–15.

    Article  PubMed  CAS  Google Scholar 

  144. Lee, Y., Jeon, K., Lee, J.T., et al. (2002) MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 21, 4663–4670.

    Article  PubMed  CAS  Google Scholar 

  145. Lee, Y., Kim, M., Han, J., et al. (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23, 4051–4060.

    Article  PubMed  CAS  Google Scholar 

  146. Denli, A.M., Tops, B.B., Plasterk, R.H., et al. (2004) Processing of primary microRNAs by the Microprocessor complex. Nature. 432, 231–235.

    Article  PubMed  CAS  Google Scholar 

  147. Gregory, R.I., Yan, K.P., Amuthan, G., et al. (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature. 432, 235–240.

    Article  PubMed  CAS  Google Scholar 

  148. Han, J., Lee, Y., Yeom, K.H., et al. (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 18, 3016–3027.

    Article  PubMed  CAS  Google Scholar 

  149. Lee, Y., Ahn, C., Han, J., et al. (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature. 425, 415–419.

    Article  PubMed  CAS  Google Scholar 

  150. Han, J., Lee, Y., Yeom, K.H., et al. (2006) Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 125, 887–901.

    Article  PubMed  CAS  Google Scholar 

  151. Lund, E., Guttinger, S., Calado, A., et al. (2004) Nuclear export of microRNA precursors. Science. 303, 95–98.

    Article  PubMed  CAS  Google Scholar 

  152. Grishok, A., Pasquinelli, A.E., Conte, D., et al. (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 106, 23–34.

    Article  PubMed  CAS  Google Scholar 

  153. Hutvagner, G., McLachlan, J., Pasquinelli, A.E., et al. (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 293, 834–838.

    Article  PubMed  CAS  Google Scholar 

  154. Khvorova, A., Reynolds, A., and Jayasena, S.D. (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell. 115, 209–216.

    Article  PubMed  CAS  Google Scholar 

  155. Murchison, E.P., and Hannon, G.J. (2004). miRNAs on the move: miRNA biogenesis and the RNAi machinery. Curr. Opin. Cell Biol. 16, 223–229.

    Article  PubMed  CAS  Google Scholar 

  156. Schwarz, D.S., Hutvagner, G., Du, T., et al. (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell. 115, 199–208.

    Article  PubMed  CAS  Google Scholar 

  157. Schwab, R., Palatnik, J.F., Riester, M., et al. (2005) Specific effects of microRNAs on the plant transcriptome. Dev. Cell. 8, 517–527.

    Article  PubMed  CAS  Google Scholar 

  158. He, L., and Hannon, G.J. (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5, 522–531.

    Article  PubMed  CAS  Google Scholar 

  159. Liu, J., Valencia-Sanchez, M.A., Hannon, G.J., et al. (2005) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat. Cell Biol. 7, 719–723.

    Article  PubMed  CAS  Google Scholar 

  160. Petersen, C.P., Bordeleau, M.E., Pelletier, J., et al. (2006) Short RNAs repress translation after initiation in mammalian cells. Mol. Cell. 21, 533–542.

    Article  PubMed  CAS  Google Scholar 

  161. Pillai, R.S., Bhattacharyya, S.N., Artus, C.G., et al. (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science. 309, 1573–1576.

    Article  PubMed  CAS  Google Scholar 

  162. Sen, G.L. and Blau, H.M. (2005) Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol. 7, 633–636.

    Article  PubMed  CAS  Google Scholar 

  163. Olsen, P.H., and Ambros, V. (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 216, 671–680.

    Article  PubMed  CAS  Google Scholar 

  164. Reinhart, B.J., Slack, F.J., Basson, M., et al. (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 403, 901–906.

    Article  PubMed  CAS  Google Scholar 

  165. Reinhart, B.J., Weinstein, E.G., Rhoades, M.W., et al. (2002) MicroRNAs in plants. Genes Dev. 16, 1616–1626.

    Article  PubMed  CAS  Google Scholar 

  166. Rhoades, M.W., Reinhart, B.J., Lim, L.P., et al. (2002) Prediction of plant microRNA targets. Cell. 110, 513–520.

    Article  PubMed  CAS  Google Scholar 

  167. Brennecke, J., Hipfner, D.R., Stark, A., et al. (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 113, 25–36.

    Article  PubMed  CAS  Google Scholar 

  168. Stark, A., Brennecke, J., Russell, R.B., et al. (2003) Identification of Drosophila MicroRNA targets. PLoS Biol. 1, E60.

    Article  PubMed  Google Scholar 

  169. Lagos-Quintana, M., Rauhut, R., Meyer, J., et al. (2003) New microRNAs from mouse and human. RNA. 9, 175–179.

    Article  PubMed  CAS  Google Scholar 

  170. Lagos-Quintana, M., Rauhut, R., Yalcin, A., et al. (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol. 12, 735–739.

    Article  PubMed  CAS  Google Scholar 

  171. Stefani, G., and Slack, F.J. (2008) Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 9, 219–230.

    Article  PubMed  CAS  Google Scholar 

  172. Kanellopoulou, C., Muljo, S.A., Kung, A.L., et al. (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 19, 489–501.

    Article  PubMed  CAS  Google Scholar 

  173. Knight, S.W., and Bass, B.L. (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science. 293, 2269–2271.

    Article  PubMed  CAS  Google Scholar 

  174. Murchison, E.P., Partridge, J.F., Tam, O.H., et al. (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc. Natl. Acad. Sci. USA. 102:12135–40.

    Article  PubMed  CAS  Google Scholar 

  175. Wang, Y., Medvid, R., Melton, R. et al. (DGCR8) Is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat. Genet. 39, 380–385.

    Google Scholar 

  176. Gangaraju, V.K. and Lin, H., (2009). MicroRNAs: key regulators of stem cells. Nat. Rev. Mol. Cell Biol. 10, 116–125.

    Article  PubMed  CAS  Google Scholar 

  177. Boyer, L.A., Lee, T.I., Cole, M.F., et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 122, 947–56.

    Article  PubMed  CAS  Google Scholar 

  178. Boyer, L.A., Plath, K., Zeitlinger, J., et al. (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature. 441, 349–353.

    Article  PubMed  CAS  Google Scholar 

  179. Kim, J., Chu, J., Shen, X., et al. (2008) An extended transcriptional network for pluripotency of embryonic stem cells. Cell. 132, 1049–1061.

    Article  PubMed  CAS  Google Scholar 

  180. Lee, T.I., Jenner, R.G., Boyer, L.A., et al., (2006) Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 125, 301–313.

    Article  PubMed  CAS  Google Scholar 

  181. Marson, A., Levine, S.S., Cole, M.F., et al. (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell. 134, 521–533.

    Article  PubMed  CAS  Google Scholar 

  182. Loh, Y.H., Wu, Q., Chew, J.L., et al., (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. 38, 431–440.

    Article  PubMed  CAS  Google Scholar 

  183. Mathur, D., Danford, T.W., Boyer, L.A., et al. (2008) Analysis of the mouse embryonic stem cell regulatory networks obtained by ChIP-chip and ChIP-PET. Genome Biol. 9, R126.

    Article  PubMed  CAS  Google Scholar 

  184. Tay, Y., Zhang, J., Thomson, A.M., et al. (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature. 455, 1124–1128.

    Article  PubMed  CAS  Google Scholar 

  185. Xu, N., Papagiannakopoulos, T., Pan, G., et al. (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 137, 647–658.

    Article  PubMed  CAS  Google Scholar 

  186. Judson, R.L., Babiarz, J.E., Venere, M., et al. (2009) Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat. Biotechnol. 27, 459–461.

    Article  PubMed  CAS  Google Scholar 

  187. Goff, L.A., Boucher, S., Ricupero, C.L., et al. (2008) Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis. Exp. Hematol. 36, 1354–1369.

    Article  PubMed  CAS  Google Scholar 

  188. Lakshmipathy, U. and Hart, R.P. (2008) Concise review: MicroRNA expression in multipotent mesenchymal stromal cells. Stem Cells. 26, 356–363.

    Article  PubMed  CAS  Google Scholar 

  189. Schoolmeesters, A., Eklund, T., Leake, D., et al. (2009) Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PLoS ONE. 4, e5605.

    Article  PubMed  CAS  Google Scholar 

  190. Chang, J., Nicolas, E., Marks, D., et al. (2004) miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 1, 106–113.

    Article  PubMed  CAS  Google Scholar 

  191. Elmen, J., Lindow, M., Schutz, S., et al. (2008) LNA-mediated microRNA silencing in non-human primates. Nature. 452, 896–899.

    Article  PubMed  CAS  Google Scholar 

  192. Esau, C., Davis, S., Murray, S.F., et al. (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 3, 87–98.

    Article  PubMed  CAS  Google Scholar 

  193. Krutzfeldt, J., Rajewsky, N., Braich, R., et al. (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 438, 685–689.

    Article  PubMed  CAS  Google Scholar 

  194. Chang, J., Guo, J.T., Jiang, D., et al. (2008) Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells. J. Virol. 82, 8215–8223.

    Article  PubMed  CAS  Google Scholar 

  195. Cheung, O., Puri, P., Eicken, C., et al. (2008) Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression. Hepatology. 48, 1810–1820.

    Article  PubMed  CAS  Google Scholar 

  196. Coulouarn, C., Factor, V.M., Andersen, J.B., et al. (2009) Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 28(40), 3526–3536.

    Article  PubMed  CAS  Google Scholar 

  197. Gramantieri, L., Ferracin, M., Fornari, F., et al. (2007) Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 67, 6092–6099.

    Article  PubMed  CAS  Google Scholar 

  198. Jopling, C.L., Yi, M., Lancaster, A.M., et al. (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 309, 1577–1581.

    Article  PubMed  CAS  Google Scholar 

  199. Ladeiro, Y., Couchy, G., Balabaud, C., et al. (2008) MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology. 47, 1955–1963.

    Article  PubMed  CAS  Google Scholar 

  200. Sarasin-Filipowicz, M., Krol, J., Markiewicz, I., et al. (2009) Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med. 15, 31–33.

    Article  PubMed  CAS  Google Scholar 

  201. Hand, N.J., Master, Z.R., Le Lay, J., et al. (2009) Hepatic function is preserved in the absence of mature microRNAs. Hepatology. 49, 618–626.

    Article  PubMed  CAS  Google Scholar 

  202. Hand, N.J., Master, Z.R., Eauclaire, S.F., et al. (2009) The microRNA-30 family is required for vertebrate hepatobiliary development. Gastroenterology. 136, 1081–1090.

    Article  PubMed  CAS  Google Scholar 

  203. Rogler, C.E., Levoci, L., Ader, T., et al. (2009) MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology. 50, 575–584.

    Article  PubMed  CAS  Google Scholar 

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  1. Stem Cell Research Center and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    Yueh-Hsin Ping

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    Raghu K. Appasani

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Kuo, T.K., Ping, YH., Lee, O.K. (2011). Mesenchymal Stem Cells for Liver Regeneration. In: Appasani, K., Appasani, R. (eds) Stem Cells & Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-860-7_10

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