Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells

Journal of Cellular Physiology

Volumn 228, Issue 2, 2013, Pages 298-305

  Zhang, Zhenzhen ^a   Liu, Jianfang ^a   Liu, Yang ^a   Li, Zheng ^a   Gao, Wei Qiang ^a,b   He, Zuping ^a,b  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; ALPHA FETOPROTEIN; CYTOCHROME P450 1A2; CYTOCHROME P450 3A4; CYTOKERATIN 18; CYTOKERATIN 19; CYTOKERATIN 7; CYTOKERATIN 8; DEXAMETHASONE; GLUCOSE 6 PHOSPHATASE; ONCOSTATIN M; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); SCATTER FACTOR;

ARTICLE; CELL DIFFERENTIATION; CELL FUNCTION; CELL MATURATION; CELL TRANSFORMATION; EMBRYONIC STEM CELL; HEMATOPOIETIC STEM CELL; HUMAN; LIVER CELL; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FAILURE; MESENCHYMAL STEM CELL; NONHUMAN; ORGAN DONOR; PHENOTYPE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; SPERMATOGONIAL STEM CELL; STEM CELL; STEM CELL TRANSPLANTATION;

ANIMALS; CELL DIFFERENTIATION; FEMALE; HEPATOCYTES; HUMANS; LIVER FAILURE; MALE; MICE; RATS; STEM CELLS; TISSUE ENGINEERING;

RATTUS;

EID: 84866991340     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.24150     Document Type: Article

References (101)

1. Agarwal S, Holton KL, Lanza R. 2008. Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 26:1117-1127.
2. Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA. 2000. Hepatocytes from non-hepatic adult stem cells. Nature 406:257.
3. Almeida-Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED. 2004. Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood 104:2582-2590.
4. Arber N, Zajicek G, Ariel I. 1988. The streaming liver. II. Hepatocyte life history. Liver 8:80-87.
5. Asahina K, Fujimori H, Shimizu-Saito K, Kumashiro Y, Okamura K, Tanaka Y, Teramoto K, Arii S, Teraoka H. 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.
6. Aurich H, Sgodda M, Kaltwasser P, Vetter M, Weise A, Liehr T, Brulport M, Hengstler JG, Dollinger MM, Fleig WE, Christ B. 2009. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut 58:570-581.
7. Baba S, Heike T, Umeda K, Iwasa T, Kaichi S, Hiraumi Y, Doi H, Yoshimoto M, Kanatsu-Shinohara M, Shinohara T, Nakahata T. 2007. Generation of cardiac and endothelial cells from neonatal mouse testis-derived multipotent germline stem cells. Stem Cells 25:1375-1383.
8. Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kawamata M, Kato T, Okochi H, Ochiya T. 2008. IFATS collection: In vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 26:2705-2712.
9. Cai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H, Meng S, Chen Y, Zhou R, Song X, Guo Y, Ding M, Deng H. 2007. Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 45:1229-1239.
10. Campard D, Lysy PA, Najimi M, Sokal EM. 2008. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology 134:833-848.
11. Carraro A, Flaibani M, Cillo U, Michelotto L, Magrofuoco E, Buggio M, Abatangelo G, Cortivo R, Herrera MB, Tetta C, Elvassore N, Zavan B. 2010. A combining method to enhance the in vitro differentiation of hepatic precursor cells. Tissue Eng Part C Methods 16:1543-1551.
12. Cascio S, Zaret KS. 1991. Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation. Development 113:217-225.
13. Chen ML, Lee KD, Huang HC, Tsai YL, Wu YC, Kuo TM, Hu CP, Chang C. 2010. HNF-4alpha determines hepatic differentiation of human mesenchymal stem cells from bone marrow. World J Gastroenterol 16:5092-5103.
14. Chinzei R, Tanaka Y, Shimizu-Saito K, Hara Y, Kakinuma S, Watanabe M, Teramoto K, Arii S, Takase K, Sato C, Terada N, Teraoka H. 2002. Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology 36:22-29.
15. Choi D, Oh HJ, Chang UJ, Koo SK, Jiang JX, Hwang SY, Lee JD, Yeoh GC, Shin HS, Lee JS, Oh B. 2002. In vivo differentiation of mouse embryonic stem cells into hepatocytes. Cell Transplant 11:359-368.
16. Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlstrom H, Lendahl U, Frisen J. 2000. Generalized potential of adult neural stem cells. Science 288:1660-1663.
17. Coleman WB, Smith GJ, Grisham JW. 1994. Development of dexamethasone-inducible tyrosine aminotransferase activity in WB-F344 rat liver epithelial stemlike cells cultured in the presence of sodium butyrate. J Cell Physiol 161:463-469.
18. Conrad S, Renninger M, Hennenlotter J, Wiesner T, Just L, Bonin M, Aicher W, Buhring HJ, Mattheus U, Mack A, Wagner HJ, Minger S, Matzkies M, Reppel M, Hescheler J, Sievert KD, Stenzl A, Skutella T. 2008. Generation of pluripotent stem cells from adult human testis. Nature 456:344-349.
19. Dabeva MD, Hwang S-G, Vasa SRG. 1997. Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver. Proc Natl Acad Sci USA 94:7356-7361.
20. Dalgetty DM, Medine CN, Iredale JP, Hay DC. 2009. Progress and future challenges in stem cell-derived liver technologies. Am J Physiol Gastrointest Liver Physiol 297:G241-G248.
21. Duan Y, Ma X, Zou W, Wang C, Bahbahan IS, Ahuja TP, Tolstikov V, Zern MA. 2010. Differentiation and characterization of metabolically functioning hepatocytes from human embryonic stem cells. Stem Cells 28:674-686.
22. Duncan AW, Dorrell C, Grompe M. 2009. Stem cells and liver regeneration. Gastroenterology 137:466-481.
23. Evans MJ, Kaufman MH. 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154-156.
24. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. 2010. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893-2917.
25. Fuster J, Charco R, Llovet JM, Bruix J, Garcia-Valdecasas JC. 2005. Liver transplantation in hepatocellular carcinoma. Transpl Int 18:278-282.
26. Gai H, Nguyen DM, Moon YJ, Aguila JR, Fink LM, Ward DC, Ma Y. 2010. Generation of murine hepatic lineage cells from induced pluripotent stem cells. Differentiation 79:171-181.
27. Gallicano GI, Mishra L. 2010. Hepatocytes from induced pluripotent stem cells: A giant leap forward for hepatology. Hepatology 51:20-22.
28. Gaudio E, Carpino G, Cardinale V, Franchitto A, Onori P, Alvaro D. 2009. New insights into liver stem cells. Dig Liver Dis 41:455-462.
29. Germain L, Noel M, Gourdeau H, Marceau N. 1988. Promotion of growth and differentiation of rat ductular oval cells in primary culture. Cancer Res 48:368-378.
30. Golding M, Sarraf CE, Lalani EN, Anilkumar TV, Edwards RJ, Nagy P, Thorgeirsson SS, Alison MR. 1995. Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver. Hepatology 22:1243-1253.
31. Golestaneh N, Kokkinaki M, Pant D, Jiang J, Destefano D, Fernandez-Bueno C, Rone JD, Haddad BR, Gallicano GI, Dym M. 2009. Pluripotent stem cells derived from adult human testes. Stem Cells Dev 138:151-162.
32. Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G. 2006. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440:1199-1203.
33. Hamazaki T, Iiboshi Y, Oka M, Papst PJ, Meacham AM, Zon LI, Terada N. 2001. Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett 497:15-19.
34. Hay DC, Fletcher J, Payne C, Terrace JD, Gallagher RC, Snoeys J, Black JR, Wojtacha D, Samuel K, Hannoun Z, Pryde A, Filippi C, Currie IS, Forbes SJ, Ross JA, Newsome PN, Iredale JP. 2008. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci USA 105:12301-12306.
35. He Z, Jiang J, Kokkinaki M, Dym M. 2009. Nodal signaling via an autocrine pathway promotes proliferation of mouse spermatogonial stem/progenitor cells through Smad2/3 and Oct-4 activation. Stem Cells 27:2580-2590.
36. He Z, Jiang J, Kokkinaki M, Golestaneh N, Hofmann MC, Dym M. 2008. Gdnf upregulates c-Fos transcription via the Ras/Erk1/2 pathway to promote mouse spermatogonial stem cell proliferation. Stem Cells 26:266-278.
37. He Z, Kokkinaki M, Jiang J, Dobrinski I, Dym M. 2010. Isolation, characterization, and culture of human spermatogonia. Biol Reprod 82:363-372.
38. He ZP, Tan WQ, Tang YF, Feng MF. 2003. Differentiation of putative hepatic stem cells derived from adult rats into mature hepatocytes in the presence of epidermal growth factor and hepatocyte growth factor. Differentiation 71:281-290.
39. He ZP, Tan WQ, Tang YF, Zhang HJ, Feng MF. 2004. Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers. Cell Prolif 37:177-187.
40. Herrera MB, Bruno S, Buttiglieri S, Tetta C, Gatti S, Deregibus MC, Bussolati B, Camussi G. 2006. Isolation and characterization of a stem cell population from adult human liver. Stem Cells 24:2840-2850.
41. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L. 2011. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475:386-389.
42. Kaestner KH. 2000. The hepatocyte nuclear factor 3 (HNF3 or FOXA) family in metabolism. Trends Endocrinol Metab 11:281-285.
43. Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T. 2004. Generation of pluripotent stem cells from neonatal mouse testis. Cell 119:1001-1012.
44. Kanatsu-Shinohara M, Lee J, Inoue K, Ogonuki N, Miki H, Toyokuni S, Ikawa M, Nakamura T, Ogura A, Shinohara T. 2008. Pluripotency of a single spermatogonial stem cell in mice. Biol Reprod 78:681-687.
45. Khurana S, Mukhopadhyay A. 2008. Hematopoietic progenitors from early murine fetal liver possess hepatic differentiation potential. Am J Pathol 173:1818-1827.
46. Knight B, Yeoh GC, Husk KL, Ly T, Abraham LJ, Yu C, Rhim JA, Fausto N. 2000. Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. J Exp Med 192:1809-1818.
47. Kossack N, Meneses J, Shefi S, Nguyen HN, Chavez S, Nicholas C, Gromoll J, Turek PJ, Reijo-Pera RA. 2009. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells 27:138-149.
48. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. 2001. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369-377.
49. Kumashiro Y, Teramoto K, Shimizu-Saito K, Asahina K, Teraoka H, Arii S. 2005. Isolation of hepatocyte-like cells from mouse embryoid body cells. Transplant Proc 37:299-300.
50. Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, Yang VW, Lee OK. 2008. Stem cell therapy for liver disease: Parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 134:2111-2121.
51. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M. 2000. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229-1234.
52. Lavon N, Benvenisty N. 2005. Study of hepatocyte differentiation using embryonic stem cells. J Cell Biochem 96:1193-1202.
53. Lazaro CA, Rhim JA, Yamada Y, Fausto N. 1998. Generation of hepatocytes from oval cell precursors in culture. Cancer Res 58:5514-5522.
54. Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK. 2004. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40:1275-1284.
55. Lemire JM, Shiojiri N, Fausto N. 1991. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am J Pathol 139:535-552.
56. Li F, Liu P, Liu C, Xiang D, Deng L, Li W, Wangensteen K, Song J, Ma Y, Hui L, Wei L, Li L, Ding X, Hu Y, He Z, Wang X. 2010a. Hepatoblast-like progenitor cells derived from embryonic stem cells can repopulate livers of mice. Gastroenterology 139:2158-2169.
57. Li W, Wang D, Qin J, Liu C, Zhang Q, Zhang X, Yu X, Lahn BT, Mao FF, Xiang AP. 2010b. Generation of functional hepatocytes from mouse induced pluripotent stem cells. J Cell Physiol 222:492-501.
58. Lin N, Lin J, Bo L, Weidong P, Chen S, Xu R. 2010. Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells in an alginate scaffold. Cell Prolif 43:427-434.
59. Liu H, Kim Y, Sharkis S, Marchionni L, Jang YY. 2011. In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci Transl Med 3:82ra39.
60. Meng G, Liu S, Krawetz R, Chan M, Chernos J, Rancourt DE. 2008. A novel method for generating xeno-free human feeder cells for human embryonic stem cell culture. Stem Cells Dev 17:413-422.
61. Michalopoulos GK, DeFrances MC. 1997. Liver regeneration. Science 276:60-66.
62. Mohsin S, Shams S, Ali N, Khan G, Javaid M, Awan S, Khan SN, Riazuddin S. 2011. Enhanced hepatic differentiation of mesenchymal stem cells after pretreatment with injured liver tissue. Differentiation 81:42-48.
63. Muraca M, Gerunda G, Neri D, Vilei MT, Granato A, Feltracco P, Meroni M, Giron G, Burlina AB. 2002. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 359:317-318.
64. Nowak G, Ericzon BG, Nava S, Jaksch M, Westgren M, Sumitran-Holgersson S. 2005. Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo. Gut 54:972-979.
65. Ong SY, Dai H, Leong KW. 2006. Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture. Biomaterials 27:4087-4097.
66. Paku S, Schnur J, Nagy P, Thorgeirsson SS. 2001. Origin and structural evolution of the early proliferating oval cells in rat liver. Am J Pathol 158:1313-1323.
67. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP. 1999. Bone marrow as a potential source of hepatic oval cells. Science 284:1168-1170.
68. Ramesh TM, Ellis AW, Spear BT. 1995. Individual mouse alpha-fetoprotein enhancer elements exhibit different patterns of tissue-specific and hepatic position-dependent activities. Mol Cell Biol 15:4947-4955.
69. Roelandt P, Sancho-Bru P, Pauwelyn K, Verfaillie C. 2010. Differentiation of rat multipotent adult progenitor cells to functional hepatocyte-like cells by mimicking embryonic liver development. Nat Protoc 5:1324-1336.
70. Sancho-Bru P, Najimi M, Caruso M, Pauwelyn K, Cantz T, Forbes S, Roskams T, Ott M, Gehling U, Sokal E, Verfaillie CM, Muraca M. 2009. Stem and progenitor cells for liver repopulation: Can we standardise the process from bench to bedside? Gut 58:594-603.
71. Sancho-Bru P, Roelandt P, Narain N, Pauwelyn K, Notelaers T, Shimizu T, Ott M, Verfaillie C. 2011. Directed differentiation of murine-induced pluripotent stem cells to functional hepatocyte-like cells. J Hepatol 54:98-107.
72. Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M, Takimoto R, Iyama S, Matsunaga T, Ohtani S, Matsuura A, Hamada H, Niitsu Y. 2005. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106:756-763.
73. Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM. 2002. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109:1291-1302.
74. Seandel M, James D, Shmelkov SV, Falciatori I, Kim J, Chavala S, Scherr DS, Zhang F, Torres R, Gale NW, Yancopoulos GD, Murphy A, Valenzuela DM, Hobbs RM, Pandolfi PP, Rafii S. 2007. Generation of functional multipotent adult stem cells from GPR125+ germline progenitors. Nature 449:346-350.
75. Shen CN, Horb ME, Slack JM, Tosh D. 2003. Transdifferentiation of pancreas to liver. Mech Dev 120:107-116.
76. Shiojiri N. 1981. Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse. J Embryol Exp Morphol 62:139-152.
77. Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, North PE, Dalton S, Duncan SA. 2010. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297-305.
78. Simon L, Ekman GC, Kostereva N, Zhang Z, Hess RA, Hofmann MC, Cooke PS. 2009. Direct transdifferentiation of stem/progenitor spermatogonia into reproductive and nonreproductive tissues of all germ layers. Stem Cells 27:1666-1675.
79. Sipe JD. 2002. Tissue engineering and reparative medicine. Ann N Y Acad Sci 961:1-9.
80. Snykers S, De Kock J, Rogiers V, Vanhaecke T. 2009. In vitro differentiation of embryonic and adult stem cells into hepatocytes: State of the art. Stem Cells 27:577-605.
81. Snykers S, Vanhaecke T, Papeleu P, Luttun A, Jiang Y, Vander Heyden Y, Verfaillie C, Rogiers V. 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.
82. Song Z, Cai J, Liu Y, Zhao D, Yong J, Duo S, Song X, Guo Y, Zhao Y, Qin H, Yin X, Wu C, Che J, Lu S, Ding M, Deng H. 2009. Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 19:1233-1242.
83. Soto-Gutierrez A, Navarro-Alvarez N, Zhao D, Rivas-Carrillo JD, Lebkowski J, Tanaka N, Fox IJ, Kobayashi N. 2007. Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines. Nat Protoc 2:347-356.
84. Strom SC, Fisher RA, Rubinstein WS, Barranger JA, Towbin RB, Charron M, Mieles L, Pisarov LA, Dorko K, Thompson MT, Reyes J. 1997a. Transplantation of human hepatocytes. Transplant Proc 29:2103-2106.
85. Strom SC, Fisher RA, Thompson MT, Sanyal AJ, Cole PE, Ham JM, Posner MP. 1997b. Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation 63:559-569.
86. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, Patapoutian A, Hampton GM, Schultz PG, Hogenesch JB. 2002. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci USA 99:4465-4470.
87. Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee JH, Church GM, Forbes SJ, Iredale JP, Wilmut I. 2010. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51:329-335.
88. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.
89. Teratani T, Yamamoto H, Aoyagi K, Sasaki H, Asari A, Quinn G, Terada M, Ochiya T. 2005. Direct hepatic fate specification from mouse embryonic stem cells. Hepatology 41:836-846.
90. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:1145-1147.
91. Touboul T, Hannan NR, Corbineau S, Martinez A, Martinet C, Branchereau S, Mainot S, Strick-Marchand H, Pedersen R, Di Santo J, Weber A, Vallier L. 2010. Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51:1754-1765.
92. Turovets N, D'Amour KA, Agapov V, Turovets I, Kochetkova O, Janus J, Semechkin A, Moorman MA, Agapova L. 2011. Human parthenogenetic stem cells produce enriched populations of definitive endoderm cells after trichostatin A pretreatment. Differentiation 81:292-298.
93. Waclawczyk S, Buchheiser A, Flogel U, Radke TF, Kogler G. 2010. In vitro differentiation of unrestricted somatic stem cells into functional hepatic-like cells displaying a hepatocyte-like glucose metabolism. J Cell Physiol 225:545-554.
94. Wang X, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. 2003. The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci USA 100:11881-11888.
95. Wang Y, Yao HL, Cui CB, Wauthier E, Barbier C, Costello MJ, Moss N, Yamauchi M, Sricholpech M, Gerber D, Loboa EG, Reid LM. 2010. Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates. Hepatology 52:1443-1454.
96. Weissman IL. 2000. Stem cells: Units of development, units of regeneration, and units in evolution. Cell 100:157-168.
97. Williams R. 2006. Global challenges in liver disease. Hepatology 44:521-526.
98. Wilson JW, Leduc EH. 1958. Role of cholangioles in restoration of the liver of the mouse after dietary injury. J Pathol Bacteriol 76:441-449.
99. Yamamoto H, Quinn G, Asari A, Yamanokuchi H, Teratani T, Terada M, Ochiya T. 2003. Differentiation of embryonic stem cells into hepatocytes: Biological functions and therapeutic application. Hepatology 37:983-993.
100. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917-1920.
101. Zhang W, Li W, Liu B, Wang P, Zhang H. 2012. Efficient generation of functional hepatocyte-like cells from human fetal hepatic progenitor cells in vitro. J Cell Physiol 227:2051-2058.