Liver regenerative medicine: Advances and challenges

Cells Tissues Organs

Volumn 196, Issue 4, 2012, Pages 291-312

  Chistiakov, Dimitry A ^a  

^a PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY   (Russian Federation)

Author keywords

Hepatocytes; Scaffolds; Stem cell therapy; Tissue engineering

Indexed keywords

BIOARTIFICIAL LIVER; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; EXTRACELLULAR MATRIX; HEMATOPOIETIC STEM CELL; HUMAN; LIVER CELL; LIVER CIRRHOSIS; LIVER FUNCTION; LIVER REGENERATION; LIVER REGENERATIVE MEDICINE; LIVER TRANSPLANTATION; MESENCHYMAL STEM CELL; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW;

ADULT STEM CELLS; ANIMALS; FETAL STEM CELLS; HEPATOCYTES; HUMANS; LIVER DISEASES; LIVER REGENERATION; REGENERATIVE MEDICINE; TISSUE ENGINEERING;

EID: 84866933906     PISSN: 14226405     EISSN: 14226421     Source Type: Journal    
DOI: 10.1159/000335697     Document Type: Review

References (229)

1. Abu-Absi, S.F., J.R. Friend, L.K. Hansen, W.-S. Hu (2002) Structural polarity and functional bile canaliculi in rat hepatocyte spheroids. Exp Cell Res 274: 56-67.
2. Allen, K.J., H.E. Soriano (2001) Liver cell transplantation: the road to clinical application. J Lab Clin Med 138: 298-312.
3. Amenta, P.S., D. Harrison (1997) Expression and potential role of the extracellular matrix in hepatic ontogenesis : a review. Microsc Res Tech 39: 372-386.
4. Anderson, D.G., J.A. Burdick, R. Langer (2004) Smart biomaterials. Science 305: 1923-1924.
5. Andersson, H., A. van den Berg (2004) Microfabrication and microfluidics for tissue engineering : state of the art and future opportunities. Lab Chip 4: 98-103.
6. Aoi, T., K. Ya, M. Nakagawa, T. Ichisaka, K. Okita, K. Takahashi, T. Chiba, S. Yamanaka (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321: 699-702.
7. Asahina, K., H. Fujimori, K. Shimizu-Saito, Y. Kumashiro, K. Okamura, Y. Tanaka, K. Teramoto, S. Arii, H. Teraoka (2004) Expression of the liver-specific gene Cyp7a1 reveals hepatic differentiation in embryoid bodies derived from mouse embryonic stem cells. Genes Cells 9: 1297-1308.
8. Augst, A.D., H.J. Kong, D.J., Mooney (2006) Alginate hydrogels as biomaterials. Macromol Biosci 6: 623-633.
9. Aurich, I., L.P. Mueller, H. Aurich, J. Luetzkendorf, K. Tisljar, M.M. Dollinger, W. Schormann, J. Walldorf, J.G. Hengstler, W.E. Fleig, B. Christ (2007) Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 56: 405-415.
10. Auth, M.K., R.E. Joplin, M. Okamoto, Y. Ishida, P. McMaster, J.M. Neuberger, R.A. Blaheta, T. Voit, A.J. Strain (2001) Morphogenesis of primary human biliary epithelial cells: induction in high-density culture or by coculture with autologous human hepatocytes. Hepatology 33: 519-529.
11. Auth, M.K., D. Woitaschek, M. Beste, T. Schreiter, H.S. Kim, E. Oppermann, R.E. Joplin, U. Baumann, P. Hilgard, S. Nadalin, B.H. Markus, R.A. Blaheta (2005) Preservation of the synthetic and metabolic capacity of isolated human hepatocytes by coculture with human biliary epithelial cells. Liver Transpl 11: 410-419.
12. Azuma, H., N. Paulk, A. Ranade, C. Dorrell, M. Al-Dhalimy, E. Ellis, S. Strom, M.A. Kay, M. Finegold, M. Grompe (2007) Robust expansion of human hepatocytes in Fah-/-/ Rag2-/-/Il2rg-/-mice. Nat Biotechnol 25: 903-910.
13. Baharvand, H., S.M. Hashemi, S. Kazemi Ashtiani, A. Farrokhi (2006) Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. Int J Dev Biol 50: 645-652.
14. Baptista, P.M., M.M. Siddiqui, G. Lozier, S.R. Rodriguez, A. Atala, S. Soker (2011) The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology 53: 604-617.
15. Basma, H., A. Soto-Gutiérrez, G.R. Yannam, L. Liu, R. Ito, T. Yamamoto, E. Ellis, S.D. Carson, S. Sato, Y. Chen, D. Muirhead, N. Navarro-Alvarez, R.J. Wong, J. Roy-Chowdhury, J.L. Platt, D.F. Mercer, J.D. Miller, S.C. Strom, N. Kobayashi, I.J. Fox (2009) Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 136: 990-999.
16. Bazou, D., W.T. Coakley, A.J. Hayes, S.K. Jackson (2008). Long-term viability and proliferation of alginate-encapsulated 3-D HepG2 aggregates formed in an ultrasound trap. Toxicol In Vitro 22: 1321-1331.
17. Bettinger, C.J., K.M. Cyr, A. Matsumoto, R. Langer, J.R. Borenstein, D.L. Kaplan (2007). Silk fibroin microfluidic devices. Adv Mater 19: 2847-2850.
18. Bilir, B., J. Durham, J. Krystal, F. Karrer, D. Kumpe, A. Ostrowska (1996) Transjugular intra-portal transplantation of cryopreserved human hepatocytes in a patient with acute liver failure. Hepatology 24: 308A.
19. Bilir, B.M., D. Guinette, F. Karrer, D.A. Kumpe, J. Krysl, J. Stephens, L. McGavran, A. Ostrowska, J. Durham (2000) Hepatocyte transplantation in acute liver failure. Liver Transpl 6: 32-40.
20. Bort, R., M. Signore, K. Tremblay, J.P. Martinez Barbera, K.S. Zaret (2006) Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Dev Biol 290: 44-56.
21. Calne, R.Y., R. Williams (1968) Liver transplantation in man. I. Observations on technique and organization in five cases. Br Med J 4: 535-540.
22. Cantz, T., A.D. Sharma, A. Jochheim-Richter, L. Arseniev, C. Klein, M.P. Manns, M. Ott (2004) Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration. Cell Transplant 13: 659-666.
23. Castorina, S., T. A. Torrisi, G. Privitera, M. Panebianco (2008) Isolation of epithelial cells with hepatobiliary phenotype. Ital J Anat Embryol 113: 199-207.
24. Chalmers, A.D., J.M.W. Slack (2000) The Xenopus tadpole gut : fate maps and morphogenetic movements. Development 127: 381-392.
25. Chamuleau, R.A.F.M., P.P.C. Poyck, M.-P. van de Kerkhove (2006) Bioartificial liver : its pros and cons. Ther Apher Dial 10: 168-174.
26. Chang, R., K. Emami, A. Jeevarajan, H. Wu, W. Sun (2011) Microprinting of liver micro-organ for drug metabolism study. Methods Mol Biol 671: 219-238.
27. Chang, R., K. Emami, H. Wu, W. Sun (2010) Biofabrication of a three-dimensional liver micro-organ as an in vitro drug metabolism model. Biofabrication 2: 045004.
28. Chang, T.T., M. Hughes-Fulford (2009) Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes. Tissue Eng Part A 15: 559-567.
29. Cheng, N., E. Wauthier, L.M. Reid (2008) Mature human hepatocytes from ex vivo differentiation of alginate-encapsulated hepatoblasts. Tissue Eng Part A 14: 1-7.
30. Chinzei, R., Y. Tanaka, K. Shimizu-Saito, Y. Hara, S. Kakinuma, M. Watanabe, K. Teramoto, S. Arii, K. Takase, C. Sato, N. Terada, H. Teraoka (2002) Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology 36: 22-29.
31. Choi, D., H.J. Lee, S. Jee, S. Jin, S.K. Koo, S.S. Paik, S.C. Jung, S.Y. Hwang, K.S. Lee, B. Oh (2005) In vitro differentiation of mouse embryonic stem cells: enrichment of endodermal cells in the embryoid body. Stem Cells 23: 817-827.
32. Coleman, W.B., K.D. McCullough, G.L. Esch, R.A. Faris, D.C. Hixson, G.J. Smith, G.J Grisham (1997) Evaluation of the differentiation potential of WB-F344 rat liver epithelial stem-like cells in vivo. Differentiation to hepatocytes after transplantation into dipeptidylpeptidase-IV-deficient rat liver. Am J Pathol 151: 353-359.
33. Crapo, P.M., T.W. Gilbert, S.F. Badylak (2011) An overview of tissue and whole organ decellularization processes. Biomaterials 32: 3233-3243.
34. Dabeva, M.D., S.G. Hwang, S.R. Vasa, E. Hurston, P.M. Novikoff, D.C. Hixson, S. Gupta, D.A. Shafritz (1997) Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver. Proc Natl Acad Sci USA 94: 7356-7361.
35. Dalakas, E., P.N. Newsome, S. Boyle, R. Brown, A. Pryde, S. McCall, P.C. Hayes, W.A. Bickmore, D.J. Harrison, J.N. Plevris (2010) Bone marrow stem cells contribute to alcohol liver fibrosis in humans. Stem Cells Dev 19: 1417-1425.
36. Dan, Y.Y., K.J. Riehle, C. Lazaro, N. Teoh, J. Haque, J.S. Campbell, N. Fausto (2006) Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci USA 103: 9912-9917.
37. David, B., E. Dore, M.Y. Jaffrin, C. Legallais (2004) Mass transfers in a fluidized bed bioreactor using alginate beads for a future bioartificial liver. Int J Artif Organs 27: 284-293.
38. Dawson, D., G. Mapili, R. Erickson, S. Taqvi, K. Roy (2008) Biomaterials for stem cell differentiation. Adv Drug Deliv Rev 60: 215-228.
39. Denker, H.W. (2009) Induced pluripotent cells: how to deal with the developmental potential. Reprod Biomed Online 19: 34-37.
40. Desai, J.P., A. Pillarisetti, A.D. Brooks (2007) Engineering approaches to biomanipulation. Annu Rev Biomed Eng 9: 35-53.
41. di Bonzo, L.V., I. Ferrero, C. Cravanzola, K. Mareschi, D. Rustichell, E. Novo, F. Sanavio, S. Cannito, E. Zamara, M. Bertero, A. Davit, S. Francica, F. Novelli, S. Colombatto, F. Fagioli, M. Parola (2008) Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 57: 223-231.
42. Discher, D.E., D.J. Mooney, P.W. Zandstra (2009) Growth factors, matrices and forces combine and control stem cells. Science 324: 1673-1677.
43. Duret, C., S. Gerbal-Chaloin, J. Ramos, J.M. Fabre, E. Jacquet, F. Navarro, P. Blanc, A. Sa-Cunha, P. Maurel, M. Daujat-Chavanieu (2007) Isolation, characterization, and differentiation to hepatocyte-like cells of nonparenchymal epithelial cells from adult human liver. Stem Cells 25: 1779-1790.
44. Elcin, Y.M., V. Dixit, G. Gitnick (1998) Hepatocyte attachment on biodegradable modified chitosan membranes : in vitro evaluation for the development of liver organoids. Artif Organs 22: 837-846.
45. Elkayam, T., S. Amitay-Shaprut, M. Dvir-Ginzberg, T. Harel, S. Cohen (2006) Enhancing the drug metabolism activities of C3A-a human hepatocyte cell line-by tissue engineering within alginate scaffolds. Tissue Eng 12: 1357-1368.
46. Ellor, S., T. Shupe, B. Petersen (2008) Stem cell therapy for inherited metabolic disorders of the liver. Exp Hematol 36: 716-725.
47. Engler, A.J., S. Sen, H.L. Sweeney, D.E. Discher (2006) Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689.
48. Eurotransplant International Foundation (2010) Annual Report 2010. http://www.eurotransplant.org/cms/index.php?page=annual-reports.
49. Evarts, R.P., P. Nagy, E. Marsden, S.S. Thorgeirsson (1987) A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis 8: 1737-1740.
50. Evenou, F., S. Couderc, B. Kim, T. Fujii, Y. Sakai (2011) Microfibrillated cellulose sheets coating oxygen-permeable PDMS membranes induce rat hepatocytes 3D aggregation into stably-attached 3D hemispheroids. J Biomater Sci Polym Ed 22: 1509-1522.
51. Fang, S., Y.D. Qiu, L. Mao, X.L. Shi, D.C. Yu, Y.T. Ding (2007) Differentiation of embryoidbody cells derived from embryonic stem cells into hepatocytes in alginate microbeads in vitro. Acta Pharmacol Sin 28: 1924-1930.
52. Fausto, N. (2000) Liver regeneration. J Hepatol 32: 19-31.
53. Fausto, N., J.S. Campbell (2003) The role of hepatocytes and oval cells in liver regeneration and repopulation. Mech Dev 120 : 117-130.
54. Feng, Z.Q., X. Chu, N.P. Huang, T. Wang, Y. Wang, X. Shi, Y. Ding, Z.Z. Gu (2009) The effect of nanofibrous galactosylated chitosan scaffolds on the formation of rat primary hepatocyte aggregates and the maintenance of liver function. Biomaterials 30: 2753-2763.
55. Fisher, R.A., D. Bu, M. Thompson, J. Tisnado, U. Prasad, R. Sterling (2000) Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion. Transplantation 69: 303-307.
56. Fisher, R.A., S.C. Strom (2006) Human hepatocyte transplantation: worldwide results. Transplantation 82: 441-449.
57. Fonsato, V., M.B. Herrera, S. Buttiglieri, S. Gatti, G. Camussi, C. Tetta (2010) Use of a rotary bioartificial liver in the differentiation of human liver stem cell. Tissue Eng. Part C Methods 16: 123-132.
58. Fox, I.J., A.N. Langnas, L.W. Fristoe, M.S., M.S. Shaefer, J.E. Vogel, D.L. Antonson, J.P. Donovan, T.G. Heffron, R.S. Markin, M.F. Sorrell (1993) Successful application of extracorporeal liver perfusion: a technology whose time has come. Am J Gastroenterol 88: 1876-1881.
59. Fruhauf, J.-H., H. Mertsching, S. Giri, N.R. Fruhauf, R. Bader (2009) Porcine endogenous retrovirus released via bioartificial liver infects primary human cells. Liver Int 29: 1553-1561.
60. Fujio, K., R.P. Evarts, Z. Hu, E.R. Marsden, S.S. Thorgeirsson (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.
61. Fukuda, J., K. Okamura, K. Ishihara, H. Mizumoto, K. Nakazawa, H. Ijima, T. Kajiwara, K. Funatsu (2005) Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell source for hybrid artificial liver. Cell Transplant 14: 819-827.
62. Gai, H., D.M. Nguyen, Y.J. Moon, J.R. Aguila, L.M. Fink, D.C. Ward, Y. Ma (2010) Generation of murine hepatic lineage cells from induced pluripotent stem cells. Differentiation 79: 171-181.
63. Germain, L., M.-J. Blouin, N. Marceau (1988) Biliary epithelial and hepatocytic cell lineage relationships in embryonic rat liver as determined by the differential expression of cytokeratins, alpha-fetoprotein, albumin, and cell surface-exposed components. Cancer Res 48: 4909-4918.
64. Goodell, M.A., S. McKinney-Freeman, F.D. Camargo (2005) Isolation and characterization of side population cells. Methods Mol Biol 290: 343-352.
65. Gouon-Evans, V., L. Boussemart, P. Gadue, D. Nierhoff, C.I. Koehler, A. Kubo, D.A. Shafritz, G. Keller (2006) BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nat Biotechnol 24: 1402-1411.
66. Grisham, J.W., W.B. Coleman, G.J. Smith (1993) Isolation, culture, and transplantation of rat hepatocytic precursor (stem-like) cells. Proc Soc Exp Biol Med 204: 270-279.
67. Grossman, M., S.E. Raper, K. Kozarsky, E.A. Stein, J.F. Engelhardt, D. Muller, P.J. Lupien, J.M. Wilson (1994) Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 6: 335-341.
68. Hanada, S., N. Kojima, Y. Sakai (2008) Soluble factor dependent in vitro growth and maturation of rat fetal liver cells in a three-dimensional culture system. Tissue Eng Part A 14: 149-160.
69. Hay, D.C., J. Fletcher, C. Payne, J.D.Terrace, R.C. Gallagher, J. Snoeys, J.R. Black, D. Wojtacha, K. Samuel, Z. Hannoun, A. Pryde, C. Filippi, I.S. Currie, S.J. Forbes, J.A. Ross, P.N. Newsome, J.P. Iredale (2008) Highly efficient differentiation of hESCs to functional hepatic endoderm requires Activin A and Wnt3a signaling. Proc Natl Acad Sci USA 105: 12301-12306.
70. Herrera, M.B., S. Bruno, S. Buttiglieri, C. Tetta, S. Gatti, M.C. Deregibus, B. Bussolati, G. Camussi (2006) Isolation and characterization of a stem cell population from adult human liver. Stem Cells 24: 2840-2850.
71. Ho, Y.C., F.L. Mi, H.W. Sung, P.L. Kuo (2009) Heparin-functionalized chitosan-alginate scaffolds for controlled release of growth factor. Int J Pharm 376: 69-75.
72. Hong, H., K. Takahashi, T. Ichisaka, T. Aoi, O. Kanagawa, M. Nakagawa, K. Okita, S. Yamanaka (2009). Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460: 1132-1135.
73. Horslen, S.P., I.J. Fox (2004) Hepatocyte transplantation. Transplantation 77: 1481-1486.
74. Hou, Y.T., H. Ijima, T. Takei, K., Kawakami (2011) Growth factor/heparin-immobilized collagen gel system enhances viability of transplanted hepatocytes and induces angiogenesis. J Biosci Bioeng 112: 265-272.
75. Hu, A.B., J.Y. Cai, Q.C. Zheng,. X.Q. He, Y. Shan, Y.L. Pan, G.C. Zeng, A. Hong, Y. Dai, L.S. Li (2004) High-ratio differentiation of embryonic stem cells into hepatocytes in vitro. Liver Int 24: 237-245.
76. Hu, C., H. Li, J. Li, Z. Zhu, S. Yin, X. Hao, M. Yao, S. Zheng, J. Gu (2008) Analysis of ABCG2 expression and side population identifies intrinsic drug efflux in the HCC cell line MHCC-97L and its modulation by Akt signaling. Carcinogenesis 29: 2289-2297.
77. Huang, H., S. Hanada, N. Kojima, Y. Sakai (2006) Enhanced functional maturation of fetal porcine hepatocytes in threedimensional poly-L-lactic acid scaffolds: a culture condition suitable for engineered liver tissues in large-scale animal studies. Cell Transplant 15: 799-809.
78. Huang, P., Z. He, S. Ji, H. Sun, D. Xiang, C. Liu, Y. Hu, X. Wang, L. Hui (2011) Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475: 386-389.
79. Ikeda, S., T. Mitaka, K. Harada, S. Sugimoto, K. Hirata, Y. Mochizuki (2002) Proliferation of rat small hepatocytes after long-term cryopreservation. J Hepatol 37: 7-14.
80. Imamura, T., L. Cui, R. Teng (2004) Embryonic stem cell-derived embryoid bodies in threedimensional culture system form hepatocyte-like cells in vitro and in vivo. Tissue Eng 10: 1716-1724.
81. Inada, M., B. Benten, K. Cheng, B. Joseph, E. Berishvili, S. Badve, L. Logdberg, M. Dabeva, M., S. Gupta (2008). Stage-specific regulation of adhesion molecule expression segregates epithelial stem/progenitor cells in fetal and adult human livers. Hepatol Int 2: 50-62.
82. Iwamuro, M., T. Komaki, Y. Kubota, M. Seita, H. Kawamoto, T. Yuasa, J.M. Shahid, R.A. Hassan, W.A. Hassan, S. Nakaji, Y. Nishikawa, E. Kondo, K. Yamamoto, I.J. Fox, N. (2010) Hepatic differentiation of mouse iPS cells in vitro. Cell Transplant 19: 841-847.
83. Jang, Y.Y., M.I. Collector, S.B. Baylin, A.M. Diehl, S.J. Sharkis (2004) Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol 6: 532-539.
84. Jensen, C.H., E.I. Jauho, E. Santoni-Rugiu, U. Holmskov, B. Teisner, N. Tygstrup, H.C. Bisgaard (2004) Transit-amplifying ductular (oval) cells and their hepatocytic progeny are characterized by a novel and distinctive expression of delta-like protein/preadipocyte factor 1/fetal antigen 1. Am J Pathol 164: 1347-1359.
85. Jiang, J.L., N. Kojima, L. Guo, K. Naruse, M. Makuuchi, A. Miyajima, W. Yan, Y. Sakai (2004) Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin M, nicotinamide, and dimethyl sulfoxide. Tissue Eng 10: 1577-1586.
86. Kaji, K., K. Norrby, A. Paca, M. Mileikovsky, P. Mohseni, K. Woltjen (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458: 771-775.
87. Kamohara, Y., N. Haraguchi, K. Mimori, F. Tanaka, H. Inoue, M. Mori, T. Kanematsu (2008) The search for cancer stem cells in hepatocellular carcinoma. Surgery 144: 119-124.
88. Karbanová, J., J. Mokrý (2002) Histological and histochemical analysis of embryoid bodies. Acta Histochem 104: 361-365.
89. Karp, J.M., L.S. Ferreira, A. Khademhosseini, A.H. Kwon, J. Yeh, R.S. Langer (2006) Cultivation of human embryonic stem cells without the embryoid body step enhances osteogenesis in vitro. Stem Cells 24: 835-843.
90. Kharaziha, P., P.M. Hellström, B. Noorinayer, F. Farzaneh, K. Aghajani, F. Jafari, M. Telkabadi, M., A. Atashi, M. Honardoost, M.R. Zali, M. Soleimani (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: 1199-1205.
91. Khuu, D.N., M. Najimi, E.M. Sokal (2007) Epithelial cells with hepatobiliary phenotype: is it another stem cell candidate for healthy adult human liver? World J Gastroenterol 13: 1554-1560.
92. Kim, J.B., V. Sebastiano, G. Wu, M.J. Araúzo-Bravo, P. Sasse, L. Gentile, K. Ko, D. Ruau, M. Ehrich, D. van den Boom, J. Meyer, K. Hübner, C. Bernemann, C. Ortmeier, M. Zenke, B.K. Fleischmann, H. Zaehres, H.R. Schöler (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136: 411-419.
93. Kinasiewicz, A., A. Gautier, D. Lewinska, J. Bukowski, C. Legallais, A. Wery?ski (2007) Culture of C3A cells in alginate beads for fluidized bed bioartificial liver. Transplant Proc 39: 2911-2913.
94. Kisseleva, T., E. Gigante, D.A. Brenner (2010) Recent advances in liver stem cell therapy. Curr. Opin Gastroenterol 26: 395-402.
95. Kogler, G., S. Sensken, J.A. Airey, T. Trapp, M. Muschen, N. Feldhahn, S. Liedtke, R.V. Sorg, J. Fischer, C. Rosenbaum, S. Greschat, A. Knipper, J. Bender, O. Degistirici, J. Gao, A.I. Caplan, E.J. Colletti, G. Almeida-Porada, H.W. Muller, E. Zanjani, P. Wernet (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200: 123-135.
96. Kosuge, M., H. Takizawa, H. Maehashi, T. Matsuura, S. Matsufuji (2007) A comprehensive gene expression analysis of human hepatocellular carcinoma cell lines as components of a bioartificial liver using a radial flow bioreactor. Liver Int 27: 101-108.
97. Koyama, T., T. Ehashi, N. Ohshima, H. Miyoshi (2009) Efficient proliferation and maturation of fetal liver cells in three-dimensional culture by stimulation of oncostatin M, epidermal growth factor, and dimethyl sulfoxide. Tissue Eng Part A 15: 1099-1107.
98. Lagasse, E., H. Connors, M. Al-Dhalimy, M. Reitsma, M. Dohse, L. Osborne, X. Wang, M. Finegold, I.L. Weissman, M. Grompe (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6: 1229-1234.
99. Lavon, N. (2010) Generation of hepatocytes from human embryonic stem cells. Methods Mol Biol 640: 237-246.
100. Leclerc, E., Y. Sakai, T. Fujii (2004) Microfluidic PDMS (polydimethylsiloxane) bioreactor for large-scale culture of hepatocytes. Biotechnol Prog 20: 750-755.
101. Lee, J., M.J. Cuddihy, N.A. Kotov (2008) Threedimensional cell culture matrices: state of the art. Tissue Eng Part B 14: 61-86.
102. Lee, K.D., T.K. Kuo, J. Whang-Peng, Y.F. Chung, C.T. Lin, S.H. Chou, J.R. Chen, Y.P. Chen, Y.P., O.K. Lee (2004) In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40: 1275-1284.
103. Lemaigre, F.P. (2009) Mechanisms of liver development : concepts for understanding liver disorders and design of novel therapies. Gastroenterology 137: 62-79.
104. Levicar, N., M. Pai, N.A. Habib, P. Tait, L.R. Jiao, S.B. Marley, J..Davis, F. Dazzi, C. Smadja, S.L. Jensen, J.P. F., Apperley, M.Y. Gordon (2008) Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease. Cell Prolif 41: 115-125.
105. Linke, K., J. Schanz, J. Hansmann, T. Walles, H. Brunner, H. Mertsching (2007) Engineered liver-like tissue on a capillarized matrix for applied research. Tissue Eng 13: 2699-2707.
106. Liu, C., Z. Xia, J.T. Czernuszka (2007) Design and development of three-dimensional scaffolds for tissue engineering. Chem Eng Res Des 85: 1051-1064.
107. Liu, H., Z. Ye, Y. Kim, S. Sharkis, Y.Y. Jang (2010a) Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology 51: 1810-1819.
108. Liu, T., S. Zhang, X. Chen, G. Li, Y. Wang (2010b) Hepatic differentiation of mouse embryonic stem cells in three-dimensional polymer scaffolds. Tissue Eng Part A 16: 1115-1122.
109. Loffredo, F., R.T. Lee (2008) Therapeutic vasculogenesis : it takes two. Circ Res 103: 128-130.
110. Lorenzini, S., A. Isidori, L. Catani, A., Gramenzi, S. Talarico, F. Bonifazi, V. Giudice, R. Conte, R., M. Baccarani, M. Bernardi, S.J. Forbes, R.M. Lemoli, P. Andreone (2008) Stem cell mobilization and collection in patients with liver cirrhosis. Aliment Pharmacol Ther 27: 932-939.
111. Lü, J.M., X. Wang, C. Marin-Muller, H. Wang, P.H. Lin, Q. Yao, C. Chen (2009) Current advances in research and clinical applications of PLGA-based nanotechnology. Expert Rev Mol Diagn 9: 325-341.
112. Lyra, A.C., M.B. Soares, L.F. da Silva, M.F. Fortes, A.G. Silva, A.C. Mota, S.A. Oliveira, E.L. Braga, W.A. de Carvalho, B. Genser, R.R. dos Santos, L.G. Lyra (2007) Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease. World J Gastroenterol 13: 1067-1073.
113. Ma, X., Y. Duan, C.J. Jung, J. Wu, C.A. Vande-Voort, M.A. Zern (2008) The differentiation of hepatocyte-like cells from monkey embryonic stem cells. Cloning Stem Cells 10: 485-493.
114. Macchiarini, P., P. Jungebluth, T. Go, M.A. Asnaghi, L.E. Rees, T.A. Cogan, A. Dodson, J. Martorell, S. Bellini, P.P. Parnigotto, S.C. Dickinson, A.P. Hollander, S. Mantero, M.T. Conconi, M.A. Birchall (2008) Clinical transplantation of a tissue-engineered airway. Lancet 372: 2023-2030.
115. Malhi, H., B. Joseph, M.L. Schilsky, S. Gupta (2008) Development of cell therapy strategies to overcome copper toxicity in the LEC rat model of Wilson disease. Regen Med 3: 165-173.
116. Matsumoto, K., R. Miki, M. Nakayama, N. Tatsumi, Y. Yokouchi (2008a) Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium. Dev Biol 319: 234-247.
117. Matsumoto, K., H. Mizumoto, K. Nakazawa, H. Ijima, K. Funatsu, T. Kajiwara (2008b) Hepatic differentiation of mouse embryonic stem cells in a three-dimensional culture system using polyurethane foam. J Biosci Bioeng 105: 350-354.
118. McClelland, R., E. Wauthier, U. Uronis, L. Reid (2008) Gradients in the liver's extracellular matrix chemistry from periportal to pericentral zones: influence on human hepatic progenitors. Tissue Eng Part A 14: 59-70.
119. McLin, V.A., S.A. Rankin, A.M. Zorn (2007) Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development 134: 2207-2217.
120. Mehrabi, A., H. Fonouni, M. Wente, M. Sadeghi, C. Eisenbach, J. Encke, B.M. Schmied, M. Libicher, M. Zeier, J. Weitz, M.W. Büchler, J. Schmidt (2006) Wound complications following kidney and liver transplantation. Clin Transplant 20: 97-110.
121. Meng, Z., X. Fu, X. Chen, S. Zeng, Y. Tian, R. Jove, R. Xu, W. Huang (2010) miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice. Hepatology 52: 2148-2157.
122. Michalopoulos, G.K., W.C. Bowen, K. Mulè, D.B. Stolz (2001) Histological organization in hepatocyte organoid cultures. Am J Pathol 159: 1877-1887.
123. Milliman Research Report (2008) 2008 US organ and tissue transplant cost estimates and discussion. http : //publications.milliman.com/research/health-rr/ pdfs/2008-us-organ-tisse-RR4-1-08.pdf
124. Millis, J.M., D.C. Cronin, R. Johnson, H. Conjeevaram, C. Conlin, S. Trevino, P. Maguire (2002) Initial experience with the modified extracorporeal liver-assist device for patients with fulminant hepatic failure : system modifications and clinical impact. Transplantation 74: 1735-1746.
125. Mitaka, T., T. Kojima, T. Mizuguchi, Y. Mochizuki (1995) Growth and maturation of small hepatocytes isolated from adult rat liver. Biochem Biophys Res Commun 214: 310-317.
126. Mitaka, T., T. Mizuguchi, F. Sato, C. Mochizuki, Y. Mochizuki, (1998) Growth and maturation of small hepatocytes. J Gastroenterol Hepatol 13: S70-S77.
127. Mitaka, T., H. Ooe (2010) Characterization of hepatic-organoid cultures. Drug Metab Rev 42: 472-481.
128. Mitry, R.R., A. Dhawan, R.D. Hughes, S. Bansal, S. Lehec, C. Terry, N.D. Heaton, J.B. Karani, G. Mieli-Vergani, M. Rela (2004) One liver, three recipients: segment IV from split-liver procedures as a source of hepatocytes for cell transplantation. Transplantation 77: 1614-1616.
129. Miyazawa, M., T. Torii, Y. Toshimitsu, K. Okada, I. Koyama (2007) Hepatocyte dynamics in a three-dimensional rotating bioreactor. J Gastroenterol Hepatol 22: 1959-1964.
130. Mohamadnejad, M., K. Alimoghaddam, M. Mohyeddin-Bonab, M. Bagheri, M. Bashtar, H. Ghanaati, H. Baharvand, A. Ghavamzadeh, R. Malekzadeh (2007) Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med 10: 459-466.
131. Morsiani, E., M. Brogli, D. Galavotti, T. Bellini, D. Ricci, P. Pazzi, A.C. Puviani (2001) Longterm expression of highly differentiated functions by isolated porcine hepatocytes perfused in a radial-flow bioreactor. Artif Organs 25: 740-748.
132. Mortensen, S.A., Z.V. Fox, N.S. Kirkby, C.B. Christiansen, J.D. Lundgren (2011) Factors associated with the development of cytomegalovirus infection following solid organ transplantation. Scand J Infect Dis 43: 360-365.
133. Nahmias, Y., R.E. Schwartz, W.S. Hu, C.M. Verfaillie, D.J. Odde (2006) Endothelium-mediated hepatocyte recruitment in the establishment of liver-like tissue in vitro. Tissue Eng 12: 1627-1638.
134. Najimi, M., D.N. Khuu, P.A. Lysy, N. Jazouli, J. Abarca, C. Sempoux, E.M. Sokal (2007) Adult derived human liver mesenchymallike cells as a potential progenitors reservoir of hepatocytes? Cell Transplant 16: 717-728.
135. Naruse, K. (2005) Artificial liver support : future aspects. J Artif Organs 8: 71-76.
136. Ng, S., Y.-H. Wu, Y. Zhou (2005) Optimization of 3-D hepatocyte culture by controlling the physical and chemical properties of the extra-cellular matrices. Biomaterials 16: 3153-3163.
137. Nguyen, T.H., J. Oberholzer, J. Birraux, P. Majno, P. Morel, D. Trono (2002) Highly efficient lentiviral vector-mediated transduction of nondividing, fully reimplantable primary hepatocytes. Mol Ther 6: 199-209.
138. NHSBT (National Health Service Blood and Transplant) (2010) Transplant Activity Report 2009-2010. http://www.uktransplant.org.uk/ukt/statistics/ transplant-activity-report/current-activity-reports/ukt/activity-report-2009-10. pdf.
139. Nishikawa, M., T. Yamamoto, N. Kojima, K. Kikuo, T. Fujii, Y. Sakai (2008) Stable immobilization of rat hepatocytes as hemispheroids onto collagen-conjugated poly-dimethylsiloxane (PDMS) surfaces : importance of direct oxygenation through PDMS for both formation and function. Biotechnol Bioeng 99: 1472-1481.
140. Ober, E.A., H. Verkade, H.A. Field, D.Y. Stainier (2006) Mesodermal Wnt2b signalling positively regulates liver specification. Nature 442: 688-691.
141. Oertel, M., D.A. Shafritz (2008) Stem cells, cell transplantation and liver repopulation. Biochim Biophys Acta 1782: 61-74.
142. Oh, S.H., C.L. Ward, A. Atala, J.J. Yoo, B.S. Harrison (2009) Oxygen generating scaffolds for enhancing engineered tissue survival. Biomaterials 30: 757-762.
143. Oh, S.H., R.P. Witek, S.H. Bae, D. Zheng, Y. Jung, A.C. Piscaglia, B.E. Petersen (2007) Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/ partial hepatectomy-induced liver regeneration. Gastroenterology 132: 1077-1087.
144. Ohashi, K., T. Yokoyama, M. Yamato, H. Kuge, H. Kanehiro, M. Tsutsumi, T. Amanuma, H. Iwata, J. Yang, T. Okano, Y. Nakajima (2007) Engineering functional two-and three-dimensional liver systems in vivo using hepatic tissue sheets. Nat Med 13: 880-885.
145. Ohno, M., K. Motojima, T. Okano, A. Taniguchi (2009) Maturation of the extracellular matrix and cell adhesion molecules in layered co-cultures of HepG2 and endothelial cells. J Biochem 145: 591-597.
146. Okita, K., M. Nakagawa, H. Hyenjong, T. Ichisaka, S. Yamanaka (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322: 949-953.
147. Olsen, B.R. (1996) Role of cartilage collagens in formation of the skeleton Ann NY Acad Sci 785 : 124-130.
148. OPTN (Organ Procurement and Transplantation Network) (2009) http : //optn.transplant.hrsa.gov/latestData/rptData.asp
149. Ostrovidov, S., J. Jiang, Y. Sakai, T., Fujii (2004) Membrane-based PDMS microbioreactor for perfused 3D primary rat hepatocyte cultures. Biomed. Microdevices 6: 279-287.
150. Pai, M., D. Zacharoulis, M.N. Milicevic, S. Helmy, L.R. Jiao, N. Levicar, P. Tait, M. Scott, S.B. Marley, K. Jestice, M. Glibetic, D. Bansi, S.A. Khan, D. Kyriakou, C. Rountas, A. Thillainayagam, J.P. Nicholls, S. Jensen, J.F. Apperley, M.Y. Gordon, N.A. Habib (2008) Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol 103: 1952-1958.
151. Patzer, J.F., 2nd, G.V. Mazariegos, R. Lopez, E. Molmenti, D. Gerber, F. Riddervold, A. Khanna, W.Y. Yin, Y. Chen, V.L. Scott, S. Aggarwal, D.J. Kramer, R.A. Wagner, Y. Zhu, M.L. Fulmer, G.D. Block, B.P. Amiot (1999) Novel bioartificial liver support system: preclinical evaluation. Ann NY Acad Sci 875: 340-352.
152. Pavlic, M., K. Libiseller, M. Hermann, P. Hengster, R. Margreiter, M. Wurmm (2007) Small human hepatocytes in rotary culture for treatment of alcohol addicts? A pilot study. Alcohol Clin Exp Res 31: 729-736.
153. Petersen, B.E., W.C. Bowen , K.D. Patrene, W.M. Mars, A.K. Sullivan, N. Murase, S.S. Boggs, J.S. Greenberger, J.P. Goff (1999) Bone marrow as a potential source of hepatic oval cells. Science 284: 1168-1170.
154. Petersen, B.E., J.P. Goff, J.S. Greenberger, G.K. Michalopoulos (1998) Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology 27: 433-445.
155. Polo, J.M., S. Liu, M.E. Figueroa, W. Kulalert, S. Eminli, KY. Tan, E. Apostolou, M. Stadtfeld, Y. Li, T. Shioda, S. Natesan, A.J. Wagers, A. Melnick, T. Evans, K. Hochedlinger (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28: 848-855.
156. Poyck, P.P., G. Mareels, R. Hoekstra, A.C. van Wijk, T.V. van der Hoeven, T.M. van Gulik, P.R. Verdonck, R.A. Chamuleau (2008b) Enhanced oxygen availability improves liverspecific functions of the AMC bioartificial liver. Artif Organs 32: 116-126.
157. Poyck, P.P., A.C. van Wijk, T.V. van der Hoeven, D.R. de Waart, R.A. Chamuleau, T.M. van Gulik, R.P. Oude Elferink, R. Hoekstra (2008a) Evaluation of a new immortalized human fetal liver cell line (cBAL111) for application in bioartificial liver. J Hepatol 48: 266-275.
158. Prasad, V.K., K.G. Lucas, G.I. Kleiner, J.A. Talano, D. Jacobsohn, G. Broadwater, R. Monroy, J. Kurtzberg (2011) Efficacy and safety of ex-vivo cultured adult human mesenchymal stem cells (Prochymal TM ) in pediatric patients with aevere refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant 17: 534-541.
159. Qian, Y., L. Lanjuan, H. Jianrong, L. Jun, C. Hongcui, F. Suzhen, Y. Xia, Y. Shuhong (2003) Study of severe hepatitis treated with a hybrid artificial liver support system. Int J Artif Organs 26: 507-513.
160. Rao, M.S., A.A. Khan, N. Parveen, M.A. Habeeb, C.M. Habibullah, G. Pand (2008) Characterization of hepatic progenitors from human fetal liver during second trimester. World J Gastroenterol 14: 5730-5737.
161. Roelandt, P., K.A. Pauwelyn, P. Sancho-Bru, K. Subramanian, L. Ordovas, K. Vanuytsel, M. Geraerts, M. Firpo, R. De Vos, J. Fevery, F. Nevens, W.S. Hu, C.M. Verfaillie (2010) Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells. PLoS One 5: e12101.
162. Saito, R., Y. Ishii, R. Ito, K. Nagatsuma, K. Tanaka, M. Saito, H. Maehashi, H. Nomoto, K. Ohkawa, H. Mano, M. Aizawa, H. Hano, K. Yanaga, T. Matsuura (2011) Transplantation of liver organoids in the omentum and kidney. Artif Organs 35: 80-83.
163. Sancho-Bru, P., P. Roelandt, N. Narain, K. Pauwelyn, T. Notelaers, T. Shimizu, M. Ott, C. Verfaillie (2011) Directed differentiation of murine-induced pluripotent stem cells to functional hepatocyte-like cells. J Hepatol 54: 98-107.
164. Sasaki, K., J. Kon, T. Mizuguchi, Q. Chen, H. Ooe, H. Oshima, K. Hirata, T. Mitaka (2008) Proliferation of hepatocyte progenitor cells isolated from adult human livers in serumfree medium. Cell Transplant 17: 1221-1230.
165. Sato, Y., H. Araki, J. Kato, K. Nakamura, Y. Kawano, M. Kobune, T. Sato, K. Miyanishi, T. Takayama, M. Takahashi, R. Takimoto, S. Iyama, T. Matsunaga, S. Ohtani, A. Matsuura, H. Hamada, Y. Niitsu (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106: 756-763.
166. Sauer, I.M., J.C. Gerlach (2002) Modular extracorporeal liver support. Artif Organs 26: 703-706.
167. Schmelzer, E., L. Zhang, A. Bruce, E. Wauthier, J. Ludlow, H.L. Yao, N. Moss, A. Melhem, R. McClelland, W. Turner, M. Kulik, S, Sherwood, T. Tallheden, N. Cheng, M.E. Furth, L.M. Reid (2007) Human hepatic stem cells from fetal and postnatal donors. J Exp Med 204: 1973-1987.
168. Sekhon, S.S., X. Tan, A. Micsenyi, W.C. Bowen, S.P. Monga (2004) Fibroblast growth factor enriches the embryonic liver cultures for hepatic progenitors. Am J Pathol 164: 2229-2240.
169. Semino, C.E., J.R. Merok, G.G. Crane, G. Panagiotakos, S. Zhang (2003) Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds. Differentiation 71: 262-270.
170. Seo, M.J., S.Y. Suh, Y.C. Bae, J.S. Jung (2005) Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 328: 258-264.
171. Sgroi, A., V. Serre-Beinier, P. Morel, L. Buhler (2009) What clinical alternatives to whole liver transplantation? Current status of artificial devices and hepatocyte transplantation. Transplantation 87: 457-466.
172. Shi, G.M., Y. Xu, J. Fan, J. Zhou, X.R. Yang, S.J. Qiu, Y. Liao, W.Z. Wu, Y. Ji, A.W. Ke, Z.B. Ding, Y.Z. He, B. Wu, G.H. Yang, W.Z. Qin, W. Zhang, J. Zhu, Z.H. Min, Z.Q. Wu (2008) Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J Cancer Res Clin Oncol 134: 1155-1163.
173. Shimada, M., Y. Yamashita, S. Tanaka, K. Shirabe, K. Nakazawa, H. Ijima, R. Sakiyama, J. Fukuda, K. Funatsu, K. Sugimachi (2007) Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver. Hepatogastroenterology 54: 814-820.
174. Shin, D., C.H. Shin, J. Tucker, E.A. Ober, F. Rentzsch, K.D. Poss, M. Hammerschmidt, M.C. Mullins, D.Y. Stainier (2007) Bmp and Fgf signaling are essential for liver specification in zebrafish. Development 134: 2041-2050.
175. Sidler Pfandler, M.A., M. Hochli, D. Inderbitzin, P.J. Meier, B. Stieger (2004) Small hepatocytes in culture develop polarized transporter expression and differentiation. J Cell Sci 117: 4077-4087.
176. Si-Tayeb, K., F.K. Noto, M. Nagaoka, J. Li, M.A. Battle, C. Duris, P.E. North, S. Dalton, S.A. Duncan (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51: 297-305.
177. Smets, F., M. Najimi, E.M. Sokal (2008) Cell transplantation in the treatment of liver diseases. Pediatr Transplant 12: 6-13.
178. Sokolsky-Papkov, M., K. Agashi, A. Olaye, K. Shakesheff, A.J. Domb (2007) Polymer carriers for drug delivery in tissue engineering. Adv Drug Deliv Rev 59: 187-206.
179. Song, S., R.P. Witek, Y. Lu, Y.K. Choi, D. Zheng, M. Jorgensen, C. Li, T.R. Flotte, B.E. Petersen (2004) Ex vivo transduced liver progenitor cells as a platform for gene therapy in mice. Hepatology 40: 918-924.
180. Song, Z., J. Cai, Y. Liu, D. Zhao, J. Yong, S. Duo, X. Song, Y. Guo, Y. Zhao, Y., H. Qin, X. Yin, C. Wu, J. Che, S. Lu, M. Ding, H. Deng (2009) Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 19: 1233-1242.
181. Soriano, H., R. Wood, D. Kang, C. Ozaki, M. Finegold, F. Bishoff (1997) Hepatocellular transplantation in children with fulminant liver failure. Hepatology 26: 239A.
182. Soto-Gutierrez, A., N. Navarro-Alvarez, J. Caballero-Corbalan, N. Tanaka, N. Kobayashi (2008) Endoderm induction for hepatic and pancreatic differentiation of ES cells. Acta Med. Okayama 62: 63-68.
183. Soto-Gutierrez, A., N. Navarro-Alvarez, H. Yagi, Y. Nahmias, M.L. Yarmush, N. Kobayashi (2010) Engineering of an hepatic organoid to develop liver assist devices. Cell Transplant 19: 815-822.
184. Starzl, T.E., T.L. Marchioro, K.N. von Kaaulla, G. Hermann, R.S. Btittain, W.R. Waddell (1963) Homotransplantation of the liver in humans. Surg Gynec Obstet 117: 659-676.
185. Stevens, M.M., H.F. Qanadilo, R. Langer, V.P. Shastri (2004) A rapid-curing alginate gel system: utility in periosteum-derived cartilage tissue engineering. Biomaterials 25: 887-894.
186. Stolz, D.B., M.A. Ross, H.M. Salem, W.M. Mars, G.K. Michalopoulos, K. Enomoto (1999) Cationic colloidal silica membrane perturbation as a means of examining changes at the sinusoidal surface during liver regeneration. Am J Pathol 155: 1487-1498.
187. Strom, S.C., J.R. Chowdhury, I.J. Fox (1999) Hepatocyte transplantation for the treatment of human disease. Semin Liver Dis 19: 39-48.
188. Sung, J.H., C. Kam, M.L. Shuler (2010) A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10: 446-455.
189. Sung, J.H., M.L. Shuler (2009) A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip 9: 1385-1394.
190. Sussman, N.L., G.T. Gislason, C.A. Conlin, J.H. Kelly (1994.) The Hepatix extracorporeal liver assist device: initial clinical experience. Artif Organs 18: 390-396.
191. Suzuki, A., A. Iwana, H. Miyashita, H. Nakauchi, H. Taniguchi (2003) Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development 130: 2513-2524.
192. Tanimizu, N., A. Miyajima (2004) Notch signaling controls hepatoblast differentiation by altering the expression of liver enriched transcription factors. J Cell Sci 117: 3165-3174.
193. Tanimizu, N., A. Miyajima (2007) Molecular mechanism of liver development and regeneration Int Rev Cytol 259: 1-48.
194. Tarnowski, M., H. Koryciak-Komarska, P. Czekaj, R. Sebesta, T.M. Czekaj, K. Urbanek, W. Likus, I. Malinowska-Kolodziej, D. Plewka, G. Nowaczyk-Dura, R. Wiaderkiewicz (2007) The comparison of multipotential for differentiation of progenitor mesenchymallike stem cells obtained from livers of young and old rats. Folia Histochem Cytobiol 45: 245-254.
195. Terai, S., T. Ishikawa, K. Omori, K. Aoyama, Y. Marumoto, Y. Urata, Y. Yokoyama, K. Uchida, T. Yamasaki, Y. Fujii, K. Okita, I. Sakaida (2006) Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 24: 2292-2298.
196. Terrace, J.D., I.S. Currie, D.C. Hay, N.M. Masson, R.A. Anderson, S.J. Forbes, R.W. Parks, J.A. Ross (2007) Progenitor cell characterization and location in the developing human liver. Stem Cells Dev 16: 771-778.
197. Terrace, J.D., D.C. Hay, K. Samuel, C. Payne, R.A. Anderson, I.S. Currie, R.W. Parks, S.J. Forbes, J.A. Ross (2009) Side population cells in developing human liver are primarily haematopoietic progenitor cells. Exp Cell Res 315: 2141-2153.
198. Thorgeirsson, S.S., J.W. Grisham (2006) Hematopoietic cells as hepatocyte stem cells : a critical review of the evidence. Hepatology 43: 2-8.
199. Touboul, T., N.R. Hannan, S. Corbineau, K. Subramanian, L. Ordovas, K. Vanuytsel, M. Geraerts, M. Firpo, R. De Vos, J. Fevery, F. Nevens, W.S. Hu, C.M. Verfaillie (2010) Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51: 1754-1765.
200. Tremblay, K.D., K.S. Zaret (2005) Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol 208: 87-99.
201. Trono, D. (2000) Lentiviral vectors: turning a deadly foe into a therapeutic agent. Gene Ther 7: 20-23.
202. Turner, W.S., E. Schmelzer, R. McClelland, E. Wauthier, W. Chen, L.M. Reid (2007) Human hepatoblast phenotype maintained by hyaluronan hydrogels. J Biomed Mater Res B Appl Biomater 82: 156-168.
203. Utikal, J., J.M. Polo, M. Stadtfeld, N. Maherali, W. Kulalert, R.M. Walsh, A. Khalil, J.G. Rheinwald, K. Hochedlinger (2009) Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460: 1145-1148.
204. Uygun, B.E., G. Price, N. Saedi, M.L. Izamis, T. Berendsen, M. Yarmush, K. Uygun (2011) Decellularization and recellularization of whole livers. J Vis Exp 48: pii: 2394.
205. Uygun, B.E., A. Soto-Gutierrez, H. Yagi, M.L. Izamis, M.A. Guzzardi, C. Shulman, J. Milwid, N. Kobayashi, A. Tilles, F. Berthiaume, M. Hertl, Y. Nahmias, M.L. Yarmush, K. Uygun (2010) Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 16 : 814-820.
206. van de Kerkhove, M.P., R. Hoekstra, R.A.F.M. Chamuleau, T.M. van Gulik (2004) Clinical application of bioartificial liver support systems. Ann Surg 240: 216-230.
207. van de Kerkhove, M.P., P.P.C. Poyck, T. Deurholt, R. Hoekstra, R.A.F.M. Chamuleau, T.M. van Gulik (2005) Liver support therapy : an overview of the AMC-bioartificial liver research. Digest Surg 22: 254-264.
208. Wang, S., D. Nagrath, P.C. Chen, F. Berthiaume, M.L. Yarmush (2008) Three-dimensional primary hepatocyte culture in synthetic selfassembling peptide hydrogel. Tissue Eng Part A 14: 227-236.
209. Wang, P., M. Cong, T.H. Liu, A.T. Yang, R. Cong, P. Wu, S.Z. Tang, Y. Xu, H. Wang, B.E. Wang, J.D. Jia, H. You (2010) Primary isolated hepatic oval cells maintain progenitor cell phenotypes after two-year prolonged cultivation. J Hepatol 53: 863-871.
210. Wang, X., M. Foster, M. Al-Dhalimy, E. Lagasse, M. Finegold, M. Grompe (2003b) The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci USA 100: 11881-11888.
211. Wang, X., S. Ge, G. McNamara, Q.L. Hao, G.M. Crooks, J.A. Nolta (2003a) Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood 101: 4201-4208.
212. Wang, X., E. Montini, M. Al-Dhalimy, E. Lagasse, M. Finegold, M. Grompe (2002) Kinetics of liver repopulation after bone marrow transplantation. Am J Pathol 161: 565-574.
213. Watt, K.D., K. Burak, M. Deschênes, L. Lilly, D. Marleau, P. Marotta, A. Mason, K.M. Peltekian, E.L. Renner, E.M. Yoshida, Canadian Transplant Hepatology Outcomes Research Network (2006) Recurrent hepatitis C posttransplantation: where are we now and where do we go from here? A report from the Canadian transplant hepatology workshop. Can J Gastroenterol 20: 725-734.
214. Weigel, P.H. (1980) Characterization of the asialoglycoprotein receptor on isolated rat hepatocytes. J Biol Chem 255: 6111-6120.
215. Woltjen, K., I.P. Michael, P. Mohseni, R. Desai, M. Mileikovsky, R. Hämäläinen, R. Cowling, W. Wang, P. Liu, M. Gertsenstein, K. Kaji, H.K. Sung, A. Nagy (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458: 766-770.
216. Wu, M.H., S.B. Huang, G.B. Lee (2010) Microfluidic cell culture systems for drug research. Lab Chip 10: 939-956.
217. Wurm, M., V. Lubei, M. Caronna, M. Hermann, S. Buttiglieri, O. Bodamer, A. Muehl, C. Tetta, R. Margreiter, P. Hengster (2009) Introduction of a novel prototype bioartificial liver support system utilizing small human hepatocytes in rotary culture. Tissue Eng Part A 15: 1063-1073.
218. Wurm, M., C. Woess, K. Libiseller, B. Beer, M. Pavlic (2010) Challenging small human hepatocytes with opiates : further characterization of a novel prototype bioartificial liver. Tissue Eng Part A 16: 807-813.
219. Xiong, A., T.W. Austin, E. Lagasse (2008) Isolation of human fetal liver progenitors and their enhanced proliferation by three-dimensional coculture with endothelial cells. Tissue Eng Part A 14: 995-1006.
220. Yamashita, T., A. Budhu, M. Forgues, X.M. Wang (2007) Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res 67: 10831-10839.
221. Yamashita, T., J. Ji, A. Budhu, M. Forgues, W. Yang, H.Y. Wang, H. Jia, Q. Ye, L.X. Qin, E. Wauthier, L.M. Reid, H. Minato, M. Honda, S. Kaneko, Z.Y. Tang, X.W. Wang (2009) Ep-CAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/ progenitor cell features. Gastroenterology 136: 1012-1024.
222. Yamashita, Y., M. Shimada, E. Tsujita, K. Shirabe, H. Ijima, K. Nakazawa, R. Sakiyama, J. Fukuda, K. Funatsu, K. Sugimachi (2002) High metabolic function of primary human and porcine hepatocytes in a polyurethane foam/spheroid culture system in plasma from patients with fulminant hepatic failure. Cell Transplant 11: 379-384.
223. Yamashita, Y., M. Shimada, E. Tsujita, K. Shirabe, H. Ijima, K. Nakazawa, R. Sakiyama, J. Fukuda, K. Funatsu, K. Sugimachi (2003) Efficacy of a larger version of the hybrid artificial liver support system using a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure pig model for preclinical experiments. Cell Transplant 12: 101-107.
224. Yokoyama, T., K. Ohashi, H. Kuge, H. Kanehiro, H. Iwata, M. Yamato, Y. Nakajima (2006) In vivo engineering of metabolically active hepatic tissues in a neovascularized subcutaneous cavity. Am J Transplant 6: 50-59.
225. Yovchev, M.I., P.N. Grozdanov, H. Zhou, H. Racherla, C. Guha, M.D. Dabeva (2008) Identification of adult hepatic progenitor cells capable of repopulating injured rat liver. Hepatology 47: 636-647.
226. Yu, C.B., X.P. Pan, L.J. Li (2009) Progress in bioreactors of bioartificial livers. Hepatobiliary Pancreat Dis Int 8: 134-140.
227. Zemel, R., L. Bachmetov, D. Ad-El, A. Abraham, R. Tur-Kaspa (2009) Expression of liver-specific markers in naïve adipose-derived mesenchymal stem cells. Liver Int 29: 1326-1337.
228. Zhang, L., N. Theise, M. Chua, L.M. Reid (2008) The stem cell niche of human livers: symmetry between development and regeneration. Hepatology 48: 1598-1607.
229. Zhou, Q.J., J.Z. Shao, L.X. Xiang, R.Z. Hu, Y.L. Lu, H. Yao, L.C. Dai (2005) Generation of embryoid bodies from mouse embryonic stem cells cultured on STO feeder cells. Cell Biol Int 29: 817-825.