Hepatic stem cells and the liver’s maturational lineages: Implications for liver biology, gene expression, and cell therapies

Tissue Stem Cells

Volumn , Issue , 2006, Pages 161-214

  Schmelzer, Eva ^a   McClelland, Randall E ^a   Melhem, Aloa ^a   Zhang, Lili ^b   Yao, Hsin Lei ^a   Wauthier, Eliane ^a   Turner, William S ^a   Furth, Mark E ^c   Gerber, David ^a   Gupta, Sanjeev ^d   Reid, Lola M ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b NANJING MEDICAL UNIVERSITY   (China)

^c WAKE FOREST SCHOOL OF MEDICINE   (United States)

^d ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33749172888     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (329)

1. Zaret KS. Regulatory phases of early liver development: paradigms of organogenesis. Nat Rev Genet 2002; 3:499-512.
2. Zaret K. Early liver differentiation: genetic potentiation and multilevel growth control. Curr Opin Genet Dev 1998; 8:526-531.
3. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284:1168-1170.
4. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS. Liver from bone marrow in humans. Hepatology 2000; 32:11-16.
5. Jian Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene GD, Ortiz-Gonzalez XR, Largaespada DA, Verfaille CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418:41-49.
6. Grompe M. Adult Liver Stem Cells. In: Lanza R, Blau H, Melton DA, Moore MA, Thomas E, Verfaille C, Weissman IL, West M, eds. Handbook of stem Cells, New York: Elsevier Academic Press, 2004.
7. Grisham JW, Thorgeirsson SS. In: Potter CS, ed. Stem Cells. London: Academic Press, 1997:233-282.
8. Fausto N, Lemire JM, Shiojiri N. Cell lineages in hepatic development and the identification of progenitor cells in normal and injured liver. Proc Soc Exp Biol Med 1993; 204:237-241.
9. Fausto N. Liver regeneration. J Hepatol 2000; 32:19-31.
10. Thorgeirsson S, Factor V, Grisham J. In: Lanza R, Blau H, Melton DA, Moore DD, Thomas E, Verfaille CM, Weissman IL, West M, eds. Handbook of Stem Cells. Vol. 2. New York: Elsevier, 2004:497-512.
11. Sell S. Liver stem cells. Mod Pathol 1994; 7:105-112.
12. Zajicek G, Schwartz-Arad D, Bartfeld E. The streaming liver. V: Time and age-dependent changes of hepatocyte DNA content, following partial hepatectomy. Liver 1989; 9:164-171.
13. Zajicek G, Arber N, Schwartz-Arad D. Streaming liver. VIII: Cell production rates following partial hepatectomy. Liver 1991; 11:347-351.
14. Jungermann K. Dynamics of zonal hepatocyte heterogeneity. Perinatal development and adaptive alterations during regeneration after partial hepatectomy, starvation and diabetes. Acta Histochem Suppl 1986; 32:89-98.
15. Reid LM. Stem cell biology, hormone/matrix synergies and liver differentiation. Curr Opin Cell Biol 1990; 2:121-130.
16. Sigal SH, Brill S, Fiorino AS, Reid LM. The liver as a stem cell and lineage system. Am J Physiol 1992; 263:G139-G148.
17. Sigal S, Brill S, Fiorino A, Reid LM. In: Zern MA, Reid LM, eds. Extracellular Matrix: Chemistry, Biology, and Pathobiology with Emphasis on the Liver. New York: Marcel Dekker, 1993:507-538.
18. Brill S, Holst P, Sigal S, Zvibel I, Fiorino A, Ochs A, Somasundaran U, Reid LM. Hepatic progenitor populations in embryonic, neonatal, and adult liver. Proc Soc Exp Biol Med 1993; 204:261-269.
19. Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA. Extracellular matrix gradients in the space of Disse: relevance to liver biology [editorial]. Hepatology 1992; 15:1198-1203.
20. Sigal SH, Gupta S, Gebhard DF Jr, Holst P, Neufeld D, Reid LM. Evidence for a terminal differentiation process in the rat liver. Differentiation 1995; 59:35-42.
21. Weiss L. Histology, Cell and Tissue Biology. 5th ed. New York: Elsevier Biomedical, 1983.
22. Gebhardt R, Bellemann P, Mecke D. Metabolic and enzymatic characteristics of adult rat liver parenchymal cells in non-proliferating primary monolayer cultures. Exp Cell Res 1978; 112:431-441.
23. Gumucio JJ, ed. Hepatocyte Heterogeneity and Liver Function. Vol. 19. Madrid: Springer International, 1989.
24. Traber PG, Chianale J, Gumucio JJ. Physiologic significance and regulation of hepatocellular heterogeneity. Gastroenterology 1988; 95:1130-1143.
25. Gebhardt R, Marti U. Heterogeneous distribution of the epidermal growth factor receptor in rat liver parenchyma. Prog Histochem Cytochem 1992; 26:164-168.
26. Gebhardt R, Jonitza D. Different proliferative responses of periportal and perivenous hepatocytes to EGF. Biochem Biophys Res Commun 1991; 181:1201-1207.
27. Gebhardt R, Mecke D. Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary culture. EMBO J 1983; 2:567-570.
28. Gaasbeek Janzen JW, Gebhardt R, ten Voorde GH, Lamers WH, Charles R, Moorman AF. Heterogeneous distribution of glutamine synthetase during rat liver development. J Histochem Cytochem 1987; 35:49-54.
29. Anatskaya OV, Vinogradov AE, Kudryavtsev BN. Hepatocyte polyploidy and metabolism/life-history traits: hypotheses testing. J Theoret Biol 1994; 168:191-199.
30. Anti M, Marra G, Rapaccini GL, Rumi C, Bussa S, Fadda G, Vecchio FM, Valenti A, Percesepe A, Pompili M, et al. DNA ploidy pattern in human chronic liver diseases and hepatic nodular lesions. Flow cytometric analysis on echo-guided needle liver biopsy. Cancer 1994; 73:281-288.
31. Brodsky WY, Uryvaeva IV. Cell polyploidy: its relation to tissue growth and function. Int Rev Cytol 1977; 50:275-332.
32. Feldmann G. Liver ploidy. J Hepatol 1992; 16:7-10.
33. Gupta S. Hepatic Polyploidy and Liver Growth Control. Semin Cancer Biol 2000; 10:161-171.
34. Severin E, Willers R, Bettecken T. Flow cytometric analysis of mouse hepatocyte ploidy. II. The development of polyploidy pattern in four mice strains with different life spans. Cell Tissue Res 1984; 238:649-652.
35. Severin E, Meier EM, Willers R. Flow cytometric analysis of mouse hepatocyte ploidy. I. Preparative and mathematical protocol. Cell Tissue Res 1984; 238:643-647.
36. Rubin EM, DeRose PB, Cohen C. Comparative image cytometric DNA ploidy of liver cell dysplasia and hepatocellular carcinoma. Mod Pathol 1494; 7:677-680.
37. Liu H, DiCunto F, Imarisio S, Reid LM. Citron kinase is a cell cycle-dependent, nuclear protein required for G2/M transition of hepatocytes. J Biol Chem 2003; 278:2541-2548.
38. Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997; 276:60-66.
39. Chiarugi V, Magnelli L, Cinelli M, Basi G. Apoptosis and the cell cycle. Cell Mol Biol Res 1994; 40:603-612.
40. Tomei LD, Cope FO, eds. Apoptosis: The Molecular Basis of Cell Death. New York: Cold Spring Harbor Laboratory Press, 1991.
41. Meikrantz W, Schlegel R. Apoptosis and the cell cycle. J Cell Biochem 1995; 58:160-174.
42. Orrenius S. Apoptosis: molecular mechanisms and implications for human disease. J Intern Med 1995; 237:529-536.
43. Gomez-Lechon MJ, Barbera E, Gil R, Baguena J. Evolutive changes of ploidy and polynucleation in adult rat hepatocytes in culture. Cell Mol Biol 1981; 27:695-701.
44. Gebhardt R. Different proliferative activity in vitro of periportal and perivenous hepatocytes. Scand J Gastroenterol Suppl 1988; 151:8-18.
45. Liu H, Di Cunto F, Imarisio S, Reid LM. Citron kinase is a cell cycle-dependent, nuclear protein required for G2/M transition of hepatocytes. J Biol Chem 2003; 278:2541-2548.
46. Tateno C, Yoshizato K. Growth potential and differentiation capacity of adult rat hepatocytes in vitro. Wound Repair Regen 1999; 7:36-44.
47. Tateno C, Takai-Kajihara K, Yamasaki C, Sato H, Yoshizato K. Heterogeneity of growth potential of adult rat hepatocytes in vitro. Hepatology 2000; 31:65-74.
48. Overturf K, al-Dhalimy M, Finegold M, Grompe M. The repopulation potential of hepatocyte populations differing in size and prior mitotic expansion. Am J Pathol 1999; 155:2135-2143.
49. Braun KM, Degen JL, Sandgren EP. Hepatocyte transplantation in a model of toxin-induced liver disease: variable therapeutic effect during replacement of damaged parenchyma by donor adult liver cells. Nat Med 2000; 6:320-326.
50. Gorla GR, Malhi H, Gupta S. Polyploidy Associated with Oxidative Injury Attenuates Proliferative Potential of Cells. J Cell Sci 2001; 114:2943-2951.
51. Gebhardt R, Lindros K, Lamers WH, Moorman AF. Ear J Cell Biol 1991; 56:464-467.
52. Marti U, Gebhardt R. Acinar heterogeneity of the epidermal growth factor receptor in the liver of male rats. Eur J Cell Biol 1991; 55:158-164.
53. Gebhardt R, Alber J, Wegner H, Mecke D. Different drug metabolizing capacities in cultured periportal and pericentral hepatocytes. Biochem Pharmacol 1994; 48:761-766.
54. Volk A, Michalopoulos G, Weidner M, Gebhardt R. Different proliferative responses of periportal and pericentral rat hepatocytes to hepatocyte growth factor. Biochem Biophys Res Commun 1995; 207:578-584.
55. Lindros KO, Oinonen T, Issakainen J, Nagy P, Thorgeirsson SS. Zonal distribution of transcripts of four hepatic transcription factors in the mature rat liver. Cell Biol Toxicol 1997; 13:257-262.
56. Ogawa A, Kurita K, Ikezawa Y, Igarashi M, Kuzumaki T, Daimon M, Kato T, Yamatani K, Sasaki H. Functional localization of glucose transporter 2 in rat liver. J Histochem Cytochem 1996; 44:1231-1236.
57. Bartels H, Herbort H, Jungermann K. Predominant periportal expression of the phosphoenolpyruvate carboxykinase and tyrosine aminotransferase genes in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization. Histochemistry 1990; 94:637-644.
58. Nauck M, Wolfle D, Katz N, Jungermann K. Modulation of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and tyrosine aminotransferase by arterial and venous oxygen concentrations in hepatocyte cultures. Eur J Biochem 1981; 119:657-661.
59. Nishimura M, Yaguti H, Yoshitsugu H, Naito S, Satoh T. Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi 2003; 123: 369-375.
60. LeCluyse EL, Madan A, Hamilton G, Carroll K, DeHaan R, Parkinson A. Expression and regulation of cytochrome P450 enzymes in primary cultures of human hepatocytes. J. Biochem. Molec. Toxicol 2000; 14(4):177-188.
61. Juang JH, Bonner-Weir S, Ogawa Y, Vacanti JP, Weir GC. Outcome of subcutaneous islet transplantation improved by polymer device. Transplantation 1996; 61: 1557-1561.
62. Bartels H, Freimann S, Jungermann K. Predominant periportal expression of the phosphoenolpyruvate carboxykinase gene in liver of fed and fasted mice, hamsters and rats studied by in situ hybridization. Histochemistry 1993; 99:303-309.
63. Eilers F, Modaressi S, Jungermann K. Predominant periportal expression of the fructose 1,6-bisphosphatase gene in rat liver: dynamics during the daily feeding rhythm and starvationrefeeding cycle. Histochem Cell Biol 1995; 103:293-300.
64. Kojima T, Yamamoto M, Tobioka H, Mizuguchi T, Mitaka T, Mochizuki Y. Changes in cellular distribution of connexins 32 and 26 during formation of gap junctions in primary cultures of rat hepatocytes. Exp Cell Res 1996; 223:314-326.
65. Stumpel F, Ott T, Willecke K, Jungermann K. Connexin 32 gap junctions enhance stimulation of glucose output by glucagon and noradrenaline in mouse liver. Hepatology 1998; 28:1616-1620.
66. Seseke FG, Gardemann A, Jungermann K. Signal propagation via gap junctions, a key step in the regulation of liver metabolism by the sympathetic hepatic nerves. FEBS Lett 1992; 301:265-270.
67. Rosenberg E, Faris RA, Spray DC, Monfils B, Abreu S, Danishefsky I, Reid LM. Correlation of expression of connexin mRNA isoforms with degree of cellular differentiation. Cell Adhes Commun 1996; 4:223-235.
68. Foucrier J, Pechinot D, Rigaut JP, Feldmann G. Transferrin secretion and hepatocyte ploidy: analysis at the single cell level using a semi-automatic image analysis method. Biol Cell 1988; 62:125-131.
69. Van Noorden CJ, Vogels IM, Fronik G, Houtkooper JM, James J. Ploidy class-dependent metabolic changes in rat hepatocytes after partial hepatectomy. Exp Cell Res 1985; 161:551-557.
70. Gebhardt R, Ebert A, Bauer G. Heterogeneous expression of glutamine synthetase mRNA in rat liver parenchyma revealed by in situ hybridization and Northern blot analysis of RNA from periportal and perivenous hepatocytes. FEBS Lett 1988; 241:89-93.
71. Shiojiri N, Wada JI, Tanaka T, Noguchi M, Ito M, Gebhardt R. Heterogeneous hepatocellular expression of glutamine synthetase in developing mouse liver and in testicular transplants of fetal liver. Lab Invest 1995; 72:740-747.
72. Roskams T, Moshage H, De Vos R, Guido D, Yap P, Desmet V. Heparan sulfate proteoglycan expression in normal human liver. Hepatology 1995; 21: 950-958.
73. Arlotto MP, Parkinson A. Identification of cytochrome P450a (P450IIA1) as the principal testosterone 7 alpha-hydroxylase in rat liver microsomes and its regulation by thyroid hormones. Arch Biochem Biophys 1989; 270(2):441-457.
74. Christa L, Simon MT, Flinois JP, Gebhardt R, Brechot C, Lasserre C. Overexpression of glutamine synthetase in human primary liver cancer. Gastroenterology 1994; 106:1312-1320.
75. Gordon GJ, Coleman WB, Grisham JW. Temporal analysis of hepatocyte differentiation by small hepatocyte-like progenitor cells during liver regeneration in retrosine-exposed rats. Am J Pathol 2000; 157:771-786.
76. Xu A, Luntz T, Macdonald J, Kubota H, Hsu E, London R, Reid LM. In: Lanza R, Langer R, Vacanti J, eds. Principles of Tissue Engineering. 2nd ed. San Diego: Academic Press, 2000.
77. Jungermann K, Heilbronn R, Katz N, Sasse D. The glucose/glucose-6-phosphate cycle in the periportal and perivenous zone of rat liver. Eur J Biochem 1982; 123:429-436.
78. Jungermann K, Katz N. Functional hepatocellular heterogeneity. Hepatology 1982; 2:385-395.
79. Kuo FC, Darnell JE Jr. Evidence that interaction of hepatocytes with the collecting (hepatic) veins triggers position-specific transcription of the glutamine synthetase and ornithine aminotransferase genes in the mouse liver. Mol Cell Biol 1991; 11:6050-6058.
80. Fahrner J, Labruyere WT, Gaunitz C, Moorman AF, Gebhardt R, Lamers WH. Identification and functional characterization of regulatory elements of the glutamine synthetase gene from rat liver. Eur J Biochem 1993; 213:1067-1073.
81. Schols L, Mecke D, Gebhardt R. Reestablishment of the heterogeneous distribution of hepatic glutamine synthetase during regeneration after CCl4-intoxication. Histochemistry 1990; 94:49-54.
82. Brill S, Holst PA, Zvibel L, Fiorino A, Sigal SH, Somasundaran U, Reid LM. In: Arias IM, Boyer JL, Fausto N, Jakoby WB, Schachter D, Shafritz DA, eds. Liver Biology and Pathobiology. 3rd ed. New York: Raven Press, 1994:869-897.
83. Macdonald JM, Xu ASL, Hiroshi K, LeCluyse E, Hamillton G, Liu H, Rong YW, Moss N, Lodestro C, Luntz T, Wolfe SP, Reid L. In: Lanza WL, Langer R, Vacanti J, eds. Methods of Tissue Engineering. San Diego: Academic Press, 2002:151-201.
84. Gupta S, Rajvanshi P, Sokhi RP, Vaidya S, Irani AN, Gorla GR. Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state. J Biol Chem 1999; 274:2157-2165.
85. Potten C, Wilson J. In: Lanza R, Blau H, Melton DA, Moore MA, Thomas E, Verfaille CM, Weissman IL, West M, eds. Handbook on Stem Cells. Vol. 2. New York: Elsevier, 2004: 1-12.
86. Morrison SJ, Shah NM, Anderson DJ. Regulatory mechanisms in stem cell biology. Cell 1997; 88:287-298.
87. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells cancer and cancer stem cells. Nature 2001; 414:105-111.
88. LeGasse E, Connors H, al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M. Purified hemopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000; 11:1229-1234.
89. Theise N. The Canals of Hering and Hepatic Stem cells in Humans. Hepatology 1999; 30:1425-1433.
90. Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics 2000; 24:372-376.
91. Burdon T, Smith A, Savataier P. Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 2002; 12:432-438.
92. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 1981; 78:7634-7638.
93. Fuchs E, Raghavan S. Getting under the skin of epidermal morphogenesis. Nat Rev Genet 2002; 3:199-209.
94. Antonchuk J, Sauvageau G, Humphries RK. HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 2002; 109:39-45.
95. Harley CB, Kim NW, Prowse KR, Weinrich SL, Hirsch KS, West MD, Bacchetti S, Hirte HW, Counter CM, Greider CW, et al. Telomerase, cell immortality, and cancer. Cold Spring Harbor Symp Quant Biol 1994; 59:307-315.
96. Harley CB, Villeponteau B. Telomeres and telomerase in aging and cancer. Curr Opin Genet Dev 1995; 5:249-255.
97. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279:349-352.
98. Mobest D, Goan SR, Junghahn I, Winkler J, Fichtner I, Hermann V, Becker M, de Lima-Hahn E, Henschler R. Differential kinetics of primitive hematopoietic cells assayed in vitro and in vivo during serum-free suspension culture of CD34(+) blood progenitor cells. Stem Cells 1999; 17:152-161.
99. Matsumoto K, Yoshitomi H, Rossant J, Zaret K. Liver organogenesis promoted by endothelial cells prior to vascular function. Sciencexpress 2001.
100. Matsumoto K, Yoshitomi H, Rossant J, Zaret K. Liver organogenesis promoted by endothelial cells prior to vascular function. Science 2001; 294(5542):559-563.
101. Shiojiri N. The origin of intrahepatic bile duct cells in the mouse. J Embryol Exp Morphol 1984; 79:25-39.
102. Ruebner BH, Blankenberg TA, Burrows DA, SooHoo W, Lund JK. Development and transformation of the ductal plate in the developing human liver. Pediatr Pathol 1990; 10:55-68.
103. Coffinier C, Gresh L, Fiette L, Tronche F, Schutz G, Babinet C, Pontoglio M, Yaniv M, Barra J. Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. Development 2002; 129:1829-1838.
104. Clotman F, Lannoy VJ, Reber M, Cereghini S, Cassiman D, Jacquemin P, Roskams T, Rousseau GG, Lemaigre FP. The onecut transcription factor HNF6 is required for normal development of the biliary tract. Development 2002; 129:1819-1828.
105. Fabris L, Strazzabosco M, Crosby HA, Ballardini G, Hubscher SG, Kelly DA, Neuberger JM, Strain AJ, Joplin R. Characterization and isolation of ductular cells coexpressing neural cell adhesion molecule and Bcl-2 from primary cholangiopathies and ductal plate malformations. Am J Pathol 2000; 156:1599-1612.
106. Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, Kumar A, Crawford JM. The canals of Hering and hepatic stem cells in humans. Hepatology 1999; 30:1425-1433.
107. Saxena T, Theise ND Canals of Hering: recent insights and current knowledge. Seminars in Liver Disease 2004; 24(1):43-48.
108. Suzuki A, Zheng Y-W, Kaneko S, Monodera M, Fukao K, Nakauchi H, Taniguchi H. Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol 2002; 156:173-185.
109. Shen C, Horb ME, Slack JMW, Tosh D. Transdifferentiation of pancreas to liver. Mech Dev 2003; 120:107-116.
110. Berishvili E, Liponava E, Kochlavashvili N, Kalandarishvili K, Benashvili L, Gupta S, Kakabadze Z. Heterotopic Auxiliary Liver in an Isolated and Vascularized Segment of the Small Intestine in Rats. Transplantation 2003; 75:1827-1832.
111. Grompe M. Pancreatic-hepatic switches in vivo. Mech Dev 2003; 120:99-106.
112. Overturf K, al-Dhalimy M, Ou CN, Finegold M, Grompe M. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. Am J Pathol 1997; 151: 1273-1280.
113. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M. Cell fusion is the principal source of bone-marrowderived hepatocytes. Nature 2003; 422:897-901.
114. Lucas J, Terada N. Spontaenous cell fusion. In: Lanza R, Blau H, Melton DA, Moore MA, Thomas E, Verfaillie C, Weissman I, West M, eds. Handbook of Stem Cells. Vol. 2. New York: Elsevier, 2004:153-158.
115. Grisham JW. Hepatocyte lineages: of clones, streams, patches, and nodules in the liver. Hepatology 1997; 25:250-252.
116. Fausto N. Growth factors in liver development, regeneration and carcinogenesis. Prog Growth Factor Res 1991; 3:219-234.
117. Thorgeirsson SS. Hepatic stem cells in liver regeneration. FASEB J 1996; 10:1249-1256.
118. Factor V, Radeva S, Thorgeirsson S. Origin and fate of oval cells in Dipin-induced hepatocarcinogenesis in the mouse. Am J Pathol 1994; 145:409-422.
119. Sandgren EP, Palmiter RD, Heckel JL, Daugherty CC, Brinster RL, Degen JL. Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene. Cell 1991; 66:245-256.
120. Rhim JA, Sandgren EP, Degen JL, Palmiter RD, Brinster RL. Replacement of diseased mouse liver by hepatic cell transplantation. Science 1994; 263:1149-1152.
121. Sandgren EP, Palmiter RD, Heckel JL, Brinster RL, Degen JL. DNA rearrangement causes hepatocarcinogenesis in albumin-plasminogen activator transgenic mice. Proc Natl Acad Sci USA 1992; 89:11523-11527.
122. Hixson DC, Faris RA, Thompson NL. An antigenic portrait of the liver during carcinogenesis. Pathobiology 1990; 58:65-77.
123. Dunsford H, Sell S. Production of monoclonal antibodies to preneoplastic liver cell populations induced by chemical carcinogens in rats and to transplantable Morris hepatomas. Cancer Res 1989; 49:65-77.
124. Engelhardt NV, Factor VM, Medvinsky AL, Baranov VN, Lazareva MN, Poltoranina VS. Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse. Differentiation 1993; 55:19-26.
125. Petersen BE, Grossbard B, Hatch H, Pi L, Deng J, Scott EW. Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers. Hepatology 2003; 37:632-640.
126. Sigal SH, Brill S, Reid LM, Zvibel I, Gupta S, Hixson D, Faris R, Holst PA. Characterization and enrichment of fetal rat hepatoblasts by immunoadsorption ("panning") and fluorescenceactivated cell sorting. Hepatology 1994; 19:999-1006.
127. Reid LM, Agelli M, Ochs A. Method of expanding hepatic precursor cells. U.S. Patent number 5,576,207, 1994.
128. Malhi H, Irani AL, Volenberg I, Schilsky ML, Gupta S. Early Cell Transplantation in LEC Rats Modeling Wilson’s Disease Eliminates Hepatic Copper with Reversal of Liver Disease. Gastroenterology 2002; 122: 438-447.
129. Yoshida Y, Tokusashi Y, Lee G, Ogawa K. Intrahepatic transplantation of normal hepatocytes prevents Wilson’s disease in Long-Evans cinnamon rats. Gastroenterology 1996; 111:1654-1660.
130. Irani AL, Malhi H, Slehria S, Giridhar GR, Volenberg I, Schilsky ML, Gupta S. Correction of Liver Disease Following Transplantation of Normal Rat Hepatocytes into long-Evans Cinnamon Rats Modeling Wilson’s Disease. Mol Ther 2001; 3:302-309.
131. Sigal SH, Rajvanshi P, Reid LM, Gupta S. Demonstration of differentiation in hepatocyte progenitor cells using dipeptidyl peptidase IV deficient mutant rats. Cell Mol Biol Res 1995; 41:39-47.
132. Kubota H, Reid LM. Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatiblity complex class I antigen. Proc Natl Acad Sci USA 2000; 97:12132-12137.
133. Kubota H, Reid LM. Processes for clonal growth of hepatic progenitor cells. U.S. Patent Application number 113918.500, 1999.
134. Kubota H, Reid LM. Methods of isolating bipotent hepatic progenitor cells. U.S. Patent Application number 113918.400, 1999.
135. Azuma H, Hirose T, Fujii H, Oe S, Yasuchika K, Fujikawa T, Yamaoka Y. Enrichment of hepatic progenitor cells from adult mouse liver. Hepatology 2003; 37:1385-1394.
136. Suzuki A, Zheng Y, Kondo R, Kusakabe M, Takada Y, Fukao K, Nakauchi H, Taniguchi H. Flow cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology 2000; 32:1230-1239.
137. Minguet S, Cortegano I, Gonzalo P, Martinez-Marin J, Andres B, Salas C, Melero D, Gaspar M, Marcos M. A population of c-kit(low), CD45-, TER119-hepatic cell progenitors of 11 day postcoitus mouse embryo liver reconstitutes cell-depleted liver organoids. J Clin Invest 2003; 112:1152-1163.
138. Tanimizu N, Nishikawa M, Saito H, Tsujimura T, Miyajima A. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci 2003; 116: 1775-1786.
139. Nitou M, Sugiyama Y, Ishikawa K, Shiojiri N. Purification of fetal mouse hepatoblasts by magnetic beads coated with monoclonal anti-E-cadherin antibodies and their in vitro culture. Exp Cell Res 2002; 279:330-343.
140. Watanabe T, Nakagawa K, Ohata S, Kitagawa D, Nishitai G, Seo J, Tanemura S, Shimizu N, Kishimoto H, Eada T, et al. SEK1/MKK4-mediated SAPK/JNK signlaing partipates in embyonic hepatoblast proliferation via pathway different from NF-KB-induced anti-apoptosis. Dev Biol 2002; 250:332-347.
141. Cho J-J, Malhi H, Wang R, Joseph B, Ludlow JW, Susick R, Gupta S. Enzymatically Labeled Chromosomal Probes for in situ Identification of Human Cells in Xenogeneic Transplant Models. Nat Med 2002; 8:1033-1036.
142. Saxen, Theise N. Seminars in Liver Disease 2004; 24(1):43-48.
143. Strain A. J. (1999) Ex vivo liver cell morphogenesis: one step nearer to the bioartificial liver? Hepatology 29(1), 288-290
144. Schmelzer E, Zhang L, Melhem A, Moss N, Wauthier E, McClelland RE, Bruce A, Yao H, Turner WS, Cheng N, Furth ME, Reid LM. Human ductal plates contain hepatic stem cells that are precursors to hepatoblasts. 2006; submitted.
145. Reid LM, Moss N, Kubota H. Human hepatic progenitors. U.S. Patent Application # 20050148072, 1999.
146. Bruce A, Zhang L, Ludlow J, Schmelzer E, Melhem A, Kulik M, Reid LM, Furth ME. Hepatic stem cells from cadaveric postnatal human liver. 2005; submitted.
147. Zhang L, Theise ND, Woosley J, Chua M, Reid L. The Stem Cell Compartment of Human Livers. 2006; In preparation.
148. McClelland R, Schmelzer E, Wauthier E, Reid L. Matrix substrata required for selfreplication of human hepatic stem cells. 2006; submitted.
149. Michalopoulos GK, Eckl PM, Cruise JL, Novicki DL, Jirtle RL. Mechanisms of rodent liver carcinogenesis. [Review] [27 refs]. Toxicol Ind Health 1987; 3:119-128.
150. Sigal SH, Rajvanshi P, Gorla GR, Sokhi RP, Saxena R, Gebhard DR Jr, Reid LM, Gupta S. Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events. Am J Physiol 1999; 276:G1260-G1272.
151. Ingber DE, Folkman J. Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol 1989; 109:317-330.
152. Reid LM. Defining hormone and matrix requirements for differntiated epithelia. In: Pollard JW, Walker JM, eds. Basic Cell Culture Protocols. Vol. 75. Chapter 21. Totowa, NJ: Humana Press, 1990:237-262.
153. Brill S, Zvibel I, Reid LM. Maturation-dependent changes in the regulation of liver-specific gene expression in embryonal versus adult primary liver cultures [published erratum appears in Differentiation. Differentiation 1995; 59:95-102.
154. Singhvi R, Stephanopoulos G, Wang DIC. Effects of substratum morphology on cell physiology. Biotech Bioeng 1943; 43:764-771.
155. Powers MJ, Rodrigueze RE, Griffith LG. Cell-substratum adhesion strength as determinant of hepatocyte aggregate morphology. Biotech Bioeng 1997; 53:415-426.
156. Mooney D, Hansen L, Vacanti J, Langer R, Farmer S, Ingber D. Switching from differentiation to growth in hepatocytes: control by extracellular matrix. J Cell Physiol 1992; 151:497-505.
157. Zern MA, Reid LM, eds. Extracellular Matrix Chemistry and Biology. New York: Academic Press, 1993.
158. Jefferson DM, Clayton DF, Darnell JE Jr, Reid LM. Post-transcriptional modulation of gene expression in cultured rat hepatocytes. Mol Cell Biol 1984; 4:1929-1934.
159. Enat R, Jefferson DM, Ruiz-Opazo N, Gatmaitan Z, Leinwand LA, Reid LM. Hepatocyte proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix. Proc Natl Acad Sci USA 1984; 81:1411-1415.
160. Susick R, Moss N, Kubota H, Leduyse E, Hamitton G, Luntz T, Ludlow J, Fair J, Gerber D, Bergstrand K, White J, Bruce A, Drury O, Gupta S, eid M. Hepatic progenitors and strategies for liver cell therapies. Ann NY Acad Sci 2001; 944:398-419.
161. Houssaint E. Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. Cell Differ 1980; 9:269-279.
162. Bossard P, Zaret KS. GATA transcription factors as potentiators of gut endoderm differentiation. Development 1998; 125:4909-4917.
163. Geller SA, Nichols WS, Kim S, Tolmachoff T, Lee S, Dycaico MJ, Felts K, Sorge JA. Hepatocarcinogenesis is the sequel to hepatitis in Z:2 alpha 1-antitrypsin transgenic mice: histopathological and DNA ploidy studies. Hepatology 1994; 19:389-397.
164. Liao WS, Conn AR, Taylor JM. Changes in rat alpha 1-fetoprotein and albumin mRNA levels during fetal and neonatal development. J Biol Chem 1980; 255:10036-10039.
165. Schmid P, Schulz WA. Coexpression of the c-myc protooncogene with alpha-fetoprotein and albumin in fetal mouse liver. Differentiation 1990; 45:96-102.
166. Sellem CH, Frain M, Erdos T, Sala-Trepat JM. Differential expression of albumin and alphafetoprotein genes in fetal tissues of mouse and rat. Dev Biol 1984; 102:51-60.
167. Sell S, Longley MA, Boulter J. alpha-Fetoprotein and albumin gene expression in brain and other tissues of fetal and adult rats. Brain Res 1985; 354:49-53.
168. Evarts RP, Nagy P, Marsden E, Thorgeirsson SS. A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis 1987; 8:1737-1740.
169. Rossi JM, Dunn NR, Hogan BL, Zaret KS. Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev 2001; 15:1998-2009.
170. Fennekohl A, Schieferdecker HL, Jungermann K, Puschel GP. Differential expression of prostanoid receptors in hepatocytes, Kupffer cells, sinusoidal endothelial cells and stellate cells of rat liver. J Hepatol 1999; 30:38-47
171. Deutsch G, Jung J, Zheng M, Lora J, Zaret KS. A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 2001; 128:871-881.
172. Burke Z, Oliver G. Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mech Dev 2002; 118:147-155.
173. Sosa-Pineda B, Wigle JT, Oliver G. Hepatocyte migration during liver development requires Prox1. Nat Genet 2000; 25:254-255.
174. Hromas R, Radich J, Collins S. PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells. Biochem Biophys Res Commun 1993; 195:976-983.
175. Martinez Barbera JP, Clements M, Thomas P, Rodriguez T, Meloy D, Kioussis D, Beddington RS. The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation. Dev Suppl 2000; 127:2433-2445.
176. Keng VW, Yagi H, Ikawa M, Nagano T, Myint Z, Yamada K, Tanaka T, Sato A, Muramatsu I, Okabe M, Sato M, Noguchi T. Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage. Biochem Biophys Res Commun 2000; 276:1155-1161.
177. Hentsch B, Lyons I, Li R, Hartley L, Lints TJ, Adams JM, Harvey RP. Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut. Genes Dev 1996; 10:70-79.
178. Eferl E, Sibilia M, Hilberg F, Fuchsbichler A, Kufferath I, Guertl B, Zenz R, Wagner E, Azatloukal K. Functions of c-jun in liver development. J Cell Biol 1999; 145:1049-1061.
179. Passegue E, Jochum W, Behrens A, Ricci R, Wagner E. Jun B can substitute for jun in mouse development and cell proliferation. Nat Genet 2002; 30:158-166.
180. Watanabe T, Nakagawa K, Ohata S, Kitagawa D, Nishitai G, Seo J, Tanemura S, Shimizu N, Kishimoto H, Wada T, et al. SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kappaB-induced antiapoptosis. Dev Biol 2002; 250:332-347.
181. Brenner DA, Koch KS, Leffert HL. Transforming growth factor-alpha stimulates proto-oncogene c-jun expression and a mitogenic program in primary cultures of adult rat hepatocytes. DNA 1989; 8:279-285.
182. Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature 1995; 376:167-170.
183. Doi TS, Marino MW, Takahashi T, Yoshida T, Sakakura T, Old LJ, Obata Y. Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc Natl Acad Sci USA 1999; 96:2994-2999.
184. Enomoto H, Yoshida K, Kishima Y, Kinoshita T, Yamamoto M, Everett A, Miyajima A, Nakamura H. Hepatoma-derived growth factor is highly expressed in developing liver and promotes fetal hepatocyte proliferation. Hepatology 2002; 36:1519-1527.
185. Schrem H, Klempnauer J, Borlak J. Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver-specific gene expression. Pharmacol Rev 2002; 54:129-158.
186. Van den Hoff MJ, Vermeulen JL, De Boer PA, Lamers WH, Moorman AF. Developmental changes in the expression of the liver-enriched transcription factors LF-B1, C/EBP, DBP and LAP/LIP in relation to the expression of albumin, alpha-fetoprotein, carbamoylphosphate synthase and lactase mRNA. Histochem J 1994; 26:20-31.
187. Nagy P, Bisgaard HC, Thorgeirsson SS. Expression of hepatic transcription factors during liver development and oval cell differentiation. J Cell Biol 1994; 126:223-233.
188. Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon JI, Landschulz WH, McKnight SL. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev 1989; 3:1146-1156.
189. Tomizawa M, Garfield S, Factor VM, Xanthopoulos K. Hepatocytes deficient in CCAAT/Enhancer binding protein alpha(C/EBPalpha)exhibit both hepatocyte and biliary epithelial cell character. Biochem Biophys Res Commun 1998; 249:1-5.
190. Wang ND, Finegold MJ, Bradley A, Ou CN, Abdelsayed SV, Wilde MD, Taylor LR, Wilson DR, Darlington GJ. Impaired energy homeostasis in C/EBP alpha knockout mice. Science 1995; 269:1108-1112.
191. Li J, Ning G, Duncan SA. Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev 2000; 14:464-474.
192. Suzuki A, Iwama A, Miyashita H, Nakauchi H, Taniguchi H. Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development 2003; 130: 2513-2524.
193. Kaestner KH, Hiemisch H, Schutz G. Targeted disruption of the gene encoding hepatocyte nuclear factor 3gamma results in reduced transcription of hepatocyte-specific genes. Mol Cell Biol 1998; 18:4245-4251.
194. Buendia MA. Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and distinctive aspects. Med Pediatr Oncol 2002; 39:530-535.
195. Aberle H, Schwartz H, Kemler R. Cadherin-catenin complex: protein interactions and their implications for cadherin function. J Cell Biochem 1996; 61:514-523.
196. Tatsuka M, Katayama H, Ota T, Tanaka T, Odashima S, Suzuki F, Terada Y. Multinuclearity and increased ploidy caused by overexpression of the aurora-and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res 1998; 58:4811-4816.
197. Monga SP, Monga HK, Tan X, Mule K, Pediaditakis P, Michalopoulos GK. Beta-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification. Gastroenterology 2003; 124:202-216.
198. Evarts RP, Nagy P, Nakatsukasa H, Marsden E, Thorgeirsson SS. In vivo differentiation of rat liver oval cells into hepatocytes. Cancer Res 1989; 49: 1541-1547.
199. Bisgaard HC, Muller S, Nagy P, Rasmussen LJ, Thorgeirsson SS. Modulation of the gene network connected to interferon-gamma in liver regeneration from oval cells. Am J Pathol 1999; 155:1075-1085.
200. Cantz T, Zuckerman DM, Burda MR, Dandri M, Goricke B, Thalhammer S, Heckl WM, Manns MP, Petersen J, Ott M. Quantitative gene expression analysis reveals transition of fetal liver progenitor cells to mature hepatocytes after transplantation in uPA/RAG-2 mice. Am J Pathol 2003; 162:37-45.
201. Weigmann A, Corbeil D, Hellwig A, Huttner WB. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci USA 1997; 94: 12425-12430.
202. Corbeil D, Roper K, Hannah MJ, Hellwig A, Huttner WB. Selective location of the polytopic membrane protein prominin in microvilli of epithelial cells-a combination of apical sorting and retention in plasma membrane protrusion. J Cell Sci 1999; 112:1023-1033.
203. Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W, Sharpe M, Gherardi E, Birchmeier C. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995; 373:699-702.
204. de Juan C, Sanchez A, Nakamura T, Fabregat I, Benito M. Hepatocyte growth factor up-regulates met expression in rat fetal hepatocytes in primary culture. Biochem Biophys Res Commun 1994; 204:1364-1370.
205. Hunt T, Luca FC, Ruderman JV. The requirements for protein synthesis and degradation, and the control of destruction of cyclins A and B in the meiotic and mitotic cell cycles of the clam embryo. J Cell Biol 1992; 116:707-724.
206. Pibiri M, Ledda-Columbano GM, Cossu C, Simbula G, Menegazzi M, Shinozuka H, Columbano A. Cyclin D1 is an early target in hepatocyte proliferation induced by thyroid hormone (T3). FASEB J 2001; 15:1006-1013.
207. Nelsen CJ, Rickheim DG, Timchenko NA, Stanley MW, Albrecht JH. Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo. Cancer Res 2001; 61:8564-8568.
208. Matsui T, Kinoshita T, Hirano T, Yokota T, Miyajima A. STAT3 down-regulates the expression of cyclin D during liver development. J Biol Chem 2002; 277: 36167-36173.
209. Crosby HA, Kelly DA, Strain AJ. Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium. Gastroenterology 2001; 120:534-544.
210. Petersen BE, Goff JP, Greenberger JS, Michalopoulos GK. Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology 1998; 27:433-445.
211. Omori M, Evarts RP, Omori N, Hu Z, Marsden ER, Thorgeirsson SS. Expression of alphafetoprotein and stem cell factor/c-kit system in bile duct ligated young rats. Hepatology 1997; 25:1115-1122.
212. Fiegel HC, Kluth J, Lioznov MV, Holzhuter S, Fehse B, Zander AR, Kluth D. Hepatic lineages isolated from developing rat liver show different ways of maturation. Biochem Biophys Res Commun 2003; 305:46-53.
213. Kubota H, Storms RW, Reid LM. Variant forms of alpha-fetoprotein transcripts expressed in human hemopoietic progenitors. J Biol Chem 2002; 277:27629-27635.
214. Taniguchi H, Suzuki A, Zheng R, Kondon Y, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao K, Nakauchi H. Usefullness of flow-cytometric cell sorting for enrichment of hepatic stem and progenitor cells in the liver. Transplant Proc 2000; 32:249-251.
215. Teyssier-Le Discorde M, Prost S, Nandrot E, Kirszenbaum M. Spatial and temporal mapping of c-kit and its ligand, stem cell factor expression during human embryonic haemopoiesis. Br J Haematol 1999; 107: 247-253.
216. Fujio K, Hu Z, Evarts RP, Marsden ER, Niu CH, Thorgeirsson SS. Coexpression of stem cell factor and c-kit in embryonic and adult liver. Exp Cell Res 1996; 224:243-250.
217. Baumann U, Crosby HA, Ramani P, Kelly DA, Strain AJ. Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: identification of a human hepatic progenitor cell? Hepatology 1999; 30:112-117.
218. Suzuki A, Zheng Y-W, Fukao K, Nakauchi K, Tniguchi H. Hepatic stem/progenitor cells with high proliferative potential in liver organ formation. Transplant Proc 2001; 33: 585-586.
219. Matsusaka S, Tsujimura T, Toyosaka A, Nakasho H, Sugihara A, Okamoto E, Uematsu K, Terada N. Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model. Hepatology 1999; 29:670-676.
220. Lian ZX, Feng B, Sugiura K, Inaba M, Yu CZ, Jin TN, Fan TX, Cui YZ, Yasumizu R, Toki J, Adachi Y, Hisha H, Ikehara S. c-kit(< low) pluripotent hemopoietic stem cells form CFU-S on day 16. Stem Cells 1999; 17:39-44.
221. Matsusaka S, Tsujimura T, Toyosaka A, Nakasho K, Sugihara A, Okamoto E, Uematsu K, Terada N. Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model. Hepatology 1999; 29:670-676.
222. Baumann U, Crosby HA, Ramani P, Kelly DA, Strain A. Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: identification of a human hepatic progenitor cell? Hepatology 1999; 30:112-117.
223. Mitchell C, Mignon A, Guidott J, Besnard S, Fabre M, Duverger N, Parlier D, Tedgui A, Kahn A, Gilgenkrantz H. Therapeutic liver repopulation in a mouse model of hypercholesterolemia. Hum Mol Genet 2000; 9:1587-1602.
224. Vrancken Peeters MJ, Patijn G, Lieber A, Perkins J, Kay M. Expansion of donor hepatocytes after recombinant adenovirus-induced liver regeneration in mice. Hepatology 1997; 25:884-888.
225. Mignon A, Guidotti J, Mitchell C, Fabre M, Wernet A, DeLaCoste A, Soubrane O, Gilgenkrantz H, Kahn A. Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes. Nat Med 1998; 4:1185-1188.
226. Thompson N, Hixson D, Callanan H, Panzica M, Flanagan D, Faris R, Hong W, Hartel-Schenk S, Doyle D. A Fischer rat substrain deficient in dipeptidyl peptidase IV activity makes normal steady-state RNA levels and an altered protein. Use as a liver-cell transplantation model. Biochem J 1991; 273:497-502.
227. Gupta S, Rajvanshi P, Lee C. Integration of transplanted hepatocytes in host liver plates demonstrated with dipeptidyl peptidase IV deficient rats. Proc Natl Acad Sci USA 1995; 92:5860-5864.
228. Rajvanshi P, Kerr A, Bhargava K, Burk R, Gupta S. Studies of liver repopulation using the dipeptidyl peptidase IV deficient rat and other rodent recipients: cell size and structure relationships regulate capacity for increased transplanted hepatocyte mass in the liver lobule. Hepatology 1996; 23:482-496.
229. Ponder KP, Gupta S, Leland F, Darlington G, Finegold M, DeMayo J, Ledley FD, Chowdhury JR, Woo SL. Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation. Proc Natl Acad Sci USA 1991; 88:1217-1221.
230. Gupta S, Aragona E, Vemuru R, Bhargava K, Burk R, Roy Chowdhury J. Permanent engraftment and function of hepatocytes delivered to the liver: implications for gene therapy and liver repopulation. Hepatology 1991; 14:144-149.
231. Sokhi R, Rajvanshi P, Gupta S. Transplanted reporter cells help in defining onset of hepatocyte proliferatin during the life of F344 rats. Am J Physiol Gastrointest Liver Physiol 2000; 279:631-640.
232. Rajvanshi P, Kerr A, Bhargava K, Burk R, Gupta S. Efficacy and safety of repeated hepatocyte transplantation for significant liver repopulation in rodents. Gastroenterology 1996; 111:1092-1102.
233. Oren R, Dabeva M, Petkov P, Hurston E, Laconi E, Shafritz D. Restoration of serum albumin levels in nagase analbuminemic rats by hepatocyte transplantation. Hepatology 1999; 29:75-81.
234. Demetriou A, Levenson S, Novikoff P, Novikoff A, Roy Chowdhury N, Whiting J, Reisner A, Roy Chowdhury J. Survival, organization and function of microcarrier-attahced hepatocytes transplanted in rats. Proc Natl Acad Sci USA 1986; 83:7475-7479.
235. Gunsalus JR, Brady D, Coulter SM, Gray B, Edge A. Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation. Nat Med 1997; 3:48-49.
236. Rhim JA, Sandgren EP, Palmiter RD, Brinster RL. Complete reconstitution of mouse liver with xenogeneic hepatocytes. Proc Natl Acad Sci USA 1995; 92:4942-4946.
237. Overturf K, al-Dhalimy M, Tanguay R, Brantly M, Ou CN, Finegold M, Grompe M. Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I [see comments] [published erratum appears in Nat Genet 1996 Apr;12(4):458]. Nat Genet 1996; 12:266-273.
238. Gagandeep S, Sokhi R, Slehria S, Gorla GR, Furgiuele J, DePinho RA, Gupta S. Hepatocyte transplantation improves survival in mice with liver toxicity induced by hepatic overexpression of Mad1 transcription factor. Mol Ther 2000; 1:358-365.
239. De Vree J, Ottenhoff R, Bosma P, Smith A, Aten J, Oude Elferink R. Correction of liver disease by hepatocyte transplantation in a mouse model of progressive failial intrahepatic cholestasis. Gastroenterology 2000; 119:1720-1730.
240. Laconi E, Oren R, Mukhopadhyay DK, Hurston E, Laconi S, Pani P, Dabeva MD, Shafritz DA. Long-term, near total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol 1998; 153:319-329.
241. Torres S, Diaz BP, Cabrera JJ, Diaz-Chico JC, Diaz-Chico BN, Lopez-Guerra A. Thyroid hormone regulation of rat hepatocyte proliferation and polyploidization. Am J Physiol 1999; 276:G155-G163.
242. Oren R, Dabeva MD, Karnezis AN, Petkov PM, Rosencrantz R, Sandhu JP, Moss SF, Wang S, Hurston E, Laconi E, Holt PR, Thung SN, Zhu L, Shafritz DA.Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes. Hepatology 1999; 30:903-913.
243. Chamuleau R. In: Mito M, Sawa M, eds. Hepatocyte Transplantation. Basel, Switzerland: Karger Landes Systems, 1999:159-167.
244. Makowka L, Rotstein L, Falk R, Falk J, Langer B, Nossal N, Blendis L, Phillips J. Reversal of toxic and anoxic induced hepatic failure by syngeneic, allogeneic and xenogeneic hepatocyte transplantation, allogeneic and xenogeneic hepatocyte transplantation. Surgery 1980; 88:2243-2253.
245. Miyazaki M, Makowka L, Falk R, Falk W, Ventura D. Reversal of lethal, chemotherapeutically induced acute hepatic necrosis in rats by regenerating liver cytosol. Surgery 1983; 94:142-150.
246. Gagandeep S, Sokhi RP, Slehria S, Gorla GR, Furgiuele J, DePinho RA, Gupta S. Hepatocyte Transplantation Improves Survival in Mice with Liver Toxicity Induced by Hepatic Overexpression of Mad1 Transcription Factor. Mol Ther 2000; 1:358-365.
247. Gagandeep S, Rajvanshi P, Sokhi RP, Slehria S, Palestro CJ, Bhargava KK, Gupta S. Transplanted hepatocytes engraft, survive, and proliferate in the liver of rats with carbon tetrachloride-induced cirrhosis. J Pathol 2000; 191:78-85.
248. Baumgartner D, LaPlante-O’Neill P, Sutherland D, Najarian J. Effects of intrasplenic injection of hepatocytes, hepatocyte fragments and hepatocyte culture supernatans on d-galactosamine-induced liver failure in rats. Eur Surg Res 1983; 15: 129-135.
249. Dabeva MD, Petkov PM, Sandhu J, Oren R, Laconi E, Hurston E, Shafritz DA. Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation in adult rat liver. Am J Pathol 2000; 156:2017-2031.
250. Sandhu J, Petcov P, Dabeva M, Shafritz D. Stem cell prop0erties and repopulation of the rat liver by fetal liver epithelial progenitor cells. Am J Pathol 2001; 159:1323-1334.
251. Suzuki A, Taniguchi H, Zheng YW, Takada Y, Fukunaga K, Seino K, Yazawa K, Otsuka M, Fukao K, Nakauchi H. Clonal colony formation of hepatic stem/progenitor cells enhanced by embryonic fibroblast conditioning medium. Transplant Proc 2000; 32:2328-2330.
252. Theise N, Badve S, Saxena R, Henegariu O, Sell S, Crawford J, Krause D. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 2000; 31:235-240.
253. Vassilopoulos G, Wang P, Russell D. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003; 422:901-904.
254. Yin Y, Lim Y, Salto-Tellez M, Ng S, Lin C, Lim S. ESC-derived cells engraft and differentiate into hepatocytes in vivo. Stem Cells 2002; 20:338-346.
255. Strick-Marchand H, Morosan S, Charneau P, Kremsdorf D, Weiss M. Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes. Proc Natl Acad Sci USA 2004; 101:8360-8365.
256. Gupta S, Chowdhary J. Hepatocyte transplantation: back to the future. Hepatology 1992; 15:156-162.
257. Gupta S, Rajvanshi P, Sokhi R, Slehria S, Yam A, Kerr A, Novikoff P. Entry and integration of transplanted hepatocytes in liver plates occur by disruption of hepatic sinusoidal endothelium. Hepatology 1999; 29:505-519.
258. Mito M, Ebata H, Kusano M, Onishi T, Saito T, Sakamoto S. Morphology and function of isolated hepatocytes transplanted into rat spleen Transplantation 1979; 28: 499-505.
259. Kusano M, Mito M. Observations on the fine structure of long-survived isolated hepatocytes inoculated into rat spleen. Gastroenterology 1982; 82:616-628.
260. Strom S, Fisher RA, Thompson MT, Sanyal AJ, Cole PE, Ham JM, Posner MT. Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation 1997; 63:559-569.
261. Grossman M, Raper S, Kozarsky K, Stein E, Engelhardt J, Muller D, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nat Genet 1994; 6:335-341.
262. Benedetti E, Kirby J, Asolati M, Blanchard J, Ward M, Williams R, Hewett T, Fontaine M, Pollak R. Intrasplenic hepatocyte allotransplantation in dalmation dogs with and without cyclosporine immunosuppression. Transplantation 1997; 63:1206-1209.
263. Gupta S, Chowdhury J. Hepatocyte transplantation. In: Arias I, Boyer J, Fausto N, Jakoby W, Schachter D, Shafritz D, eds. The Liver: Biology and Pathology. 3rd ed. New York: Raven Press, 1994:1533-1536.
264. Gupta S, Yermeni P, Vemuru R, Lee C, Yellin E, Bhargava, K. Studies on the safetyof intrasplenic hepatocyte transplantation: relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure. Hum Gene Ther 1993; 4: 249-257.
265. Brill S, Zvibel I, Halpern Z, Oren R. The role of fetal and adult hepatocyte extracellular matrix in the regulation of tissue-specific gene expression in fetal and adult hepatocytes. Eur J Cell Biol 2002; 81:43-50.
266. Xu AS, Reid LM. Soft, porous poly (D, L-lactide-co-glycotide) microcarriers designed for ex vivo studies and for transplantation of adherent cell types including progenitors. Ann N Y Acad Sci 2002; 944:144-159.
267. Mikos AG, Sarakinos G, Leite SM, Vacanti JP, Langer R. Laminated three-dimensional biodegradable foams for use in tissue engineering. Biomaterials 1993; 14:323-330.
268. Gilbert JC, Takada T, Stein JE, Langer R, Vacanti JP. Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats. Transplantation 1993; 56:423-427.
269. Langer R, Vacanti JP. Artificial organs. Sci Am 1995; 273:130-133.
270. Mooney DJ, Baldwin DF, Suh NP, Vacanti JP, Langer R. Novel approach to fabricate porous sponges of poly(D, L-lactic-co-glycolic acid) without the use of organic solvents. Biomaterials 1996; 17:1417-1422.
271. Tharakan J, Chau P. A Radial Flow Hollow Fiber Bioreactor for the Large-Scale Culture of Mammalian Cells. Biotechnol Bioeng 1986; 18:329-342.
272. Gerlach JC. Use of hepatocyte cultures for liver support bioreactors. Adv Exp Med Biol 1994; 368:165-171.
273. Catapano G, Bartolo LD. Importance of the Kinetic Characterization of Liver Cell Metabolic Reactions to the Design of Hybrid Liver Support Devices. J Artif Organs 1996; 19:670-676.
274. Nyberg S, Shatford R, Hu W, Payne W, Cerra F. Hepatocyte Culture Systems for Artificial Liver Support: Implications for Critical Care Medicine (Bioartificial Liver Support). Crit Care Med 1992; 20:1157-1168.
275. Chowdhury JR, Chowdhury NR, Strom SC, Kaufman SS, Horslen SM, Fox IJ. Human hepatocyte transplantation: gene therapy and more? Pediatrics 1998; 102:647-648.
276. Jauregui HO. In: Lanza WL, Langer R, Vacanti J, eds. Principles of Tissue Engineering. 2nd ed. San Diego: Academic Press, 2000:541-552.
277. Mullon C, Solomon BA. HepatAssist liver support system. In: Lanza R, Langer R, Vacanti J, eds. Principles of Tissue Engineering. San Diego, CA: Academic Press, 2000.
278. Macdonald JM, Griffin J, Kubota H, Griffith L, Fair J, Reid L. Bioartificial Livers. Boston: Birkhauser, 1999.
279. MacDonald JM, Wolfe SP, Roy-Chowdhury I, Kubota H, Reid LM Effect of flow configuration and membrane characteristics on membrane fouling in a novel multicoaxial hollow-fiber bioartificial liver. Ann N Y Acad Sci 2001; 944:334-343.
280. Sauer I, Zeilinger K, Pless G, Kardassis D, Theruvath T, Pascher A, Mueller A, Steinmueller T, Neuhaus P, Gerlach J. Extracorporeal liver support based on primary human liver cells and albumin dialysis-treatment of a patient with primary graft nonfunction. J Hepatol 2003; 39:649-653.
281. Gerlach J, TJorres A, Trost O, Hole O, Vienken J, Courtney J, Gahl G, Neuhaus P. Side effects of hybrid liver support therapy: TNF-alphaliberation in pigs, associated with extracorporeal bioreactors. Int J Artif Organs 1993; 16:604-608.
282. Mullon CM, Solomon BA. Hepatic Assist Liver Support System. In: Lanza WL, Langer R, Vacanti J, eds. Principles of Tissue Engineering, 2nd ed, San Diego: Academic Press, 2000; 553-558.
283. Gerlach J, Brombacher J, Courtney J, Neuhaus P. Nonenzymatic versus enzymatic hepatocyte isolation from pig livers for larger scale investigations of liver cell perfusion systems. Int J Artif Organs 1993; 16:677-681.
284. Gerlach JC, Lemmens P, Schon M, Janke J, Rossaint R, Busse B, Puhl G, Neuhaus P. Experimental evaluation of a hybrid liver support system. Transplant Proc 1997; 29:852.
285. Gerlach J. Development of a Hybrid Liver Support System: A Review. Int J Artif Organs 1996; 19:645-654.
286. Groth G, Arborgh B, Bjorken C, Sundberg B, Lundgren G. Correction of hyperbilirubinemia in the glucuronyltransferase-deficient rat by intraportal hepatocyte transplantation. Transplant Proc 1977; 9:313-316.
287. Sutherland D, Numata M, Matas A, Simons R, Najarian J. Hepatocellular transplantation in acute liver failure. Surgery 1977; 82:124-132.
288. Ribeiro J, Nordlinger B, Ballet F, Cynober L, Lucas C, Baudrimont M, et al. Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portalcaval shunted rats. Hepatology 1992; 15:12-18.
289. Soriano H, Wood R, Kang D, Ozaki C, Finegold M, Bischoff F, et al. Hepatocellular transplantation (HCT) in children with fulminant liver failure. Hepatology 1997; 30:239A.
290. Bilir B, Kumpe D, Krysl J, Guenette D, Ostrowska A, Eberson GT, Sresthra R, Lin TC, Cole W, Lear J, Durham JD. Hepatocyte transplantation in patients with liver cirrhosis. Digestive Diseases (published conference abstracts) AASLD Meetings, Abstract number LOO56, May 16-22, 1998.
291. Bilir BM, Guenette D, Karrer F, Kumpe DA, Krysl J, Stephens J, McGavran L, Ostrowska A, Durham J. Hepatocyte transplantation in acute liver failure. Liver Transplant 2000; 6:41-43.
292. Strom SC, Chowdhury JR, Fox IJ. Hepatocyte transplantation for the treatment of human disease (Review). Semin Liver Dis 1999; 19:39-48.
293. Fox IJ, Chowdhury JR, Kaufman S, Goertzen TC, Chowdhury NR, Warkentin P, Dorko K, Saulter BV, Strom S. Brief Report: Treatment of the Craigler-Najar Syndrome Type I with hepatocyte transplantation. N Engl J Med 1998; 338:1422-1426.
294. Horslen S, McCowan T, Goertzen T, Warkentin P, Strom S, IJ F. Isolated hepatocyte transplantation: a new approach to the treatment of urea cycle disorders. J Inherit Metab Dis 1999; 1(suppl):123.
295. Strom S, Fisher R, Rubinstein W, Barranger J, Towbin R, Charron M, Mieles L, Pisarov L, Dorko K, Thompson M, Reyes J. Transplantation of human hepatocytes. Transplant Proc 1997; 29:2103-2106.
296. Bohnen NL, Charron M, Reyes J, Rubinstein W, Strom SC, Swanson D, Towbin R. Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion. Clin Nucl Med 2000; 25:447-450.
297. Bilir B, Guenette D, Ostrowska A, Durham J, Kumpe D, Krystal J. Percutaneous hepatocyte transplantation in liver failure. Hepatology 1997; 26:252A.
298. Bilir B, Durham J, Krystal J. Transjugular intraportal transplantation of cryopreserved humanhepoatyctes in a patient with acute liver failure. Hepatology 1996; 24:728A.
299. Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin P, Dorko K, Sauter BV, Strom S. Treatment of the Crigler-Najjar Syndrome Type I with hepatocyte transplantation. N Engl J Med 1998; 338:1422-1426.
300. Zaret K. Developmental competence of the gut endoderm: genetic potentiation by GATA and HNF3/fork head proteins. Dev Biol (Orlando) 1999; 209:1-10.
301. Shiojiri N. Transient expression of bile-duct-specific cytokeratin in fetal mouse hepatocytes. Cell Tissue Res 1994; 278:117-123.
302. Van Eyken P, Sciot R, Desmet V. Intrahepatic bile duct development in the rat: a cytokeratinimmunohistochemical study. Lab Invest 1988; 59:52-59.
303. Ros JE, Libbrecht L, Geuken M, Jansen PL, Roskams TA. High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease. J Pathol 2003; 200:553-560.
304. Joseph B, Bhargava K, Malhi H, Schilsky ML, Jain D, Palestro C, Gupta S. Sestamibi is a Substrate for MDR1 and MDR2 P-glycoprotein Genes. Eur J Nucl Med Mol Imaging 2003; 30:1024-1031.
305. Van Den Heuvel M, Sloof M, Visser L, Muller M, De Jong K, Poppema S, Gouw A. Expression of anti-OV6 antibody and anti-N-CAM antibody along the biliary line of normal and diseased human livers. Hepatology 2001; 33:1387-1393.
306. Morrison SJ, Prowse KR, Ho P, Weissman IL. Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 1996; 5:207-216.
307. Austin TW, Solar GP, Ziegler FC, Liem L, Matthews W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood 1997; 89:3624-3635.
308. Plescia CP, Rogler CE, Rogler LE. Genomic expression analysis implicates Wnt signaling pathway and extracellular matrix alterations in hepatic specification and differentiation of murine hepatic stem cells. Differentiation 2001; 68:254-269.
309. Fujio K, Evarts RP, Hu Z, Marsden ER, Thorgeirsson SS. Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab Invest 1994; 70:511-516.
310. Kobari L, Giarratana MC, Pflumio F, Izac B, Coulombel L, Douay L. CD133+ cell selection is an alternative to CD34+ cell selection for ex vivo expansion of hematopoietic stem cells. J Hematother Stem Cell Res 2001; 10:273-281.
311. Omori N, Omori M, Evarts RP, Teramoto T, Miller MJ, Hoang TN, Thorgeirsson SS. Partial cloning of rat CD34 cDNA and expression during stem cell-dependent liver regeneration in the adult rat. Hepatology 1997; 26:720-727.
312. Lints TJ, Hartley L, Parsons LM, Harvey RP. Mesoderm-specific expression of the divergent homeobox gene Hlx during murine embryogenesis. Dev Dyn 1996; 205:457-470.
313. Rollini P, Fournier RE. The HNF-4/HNF-1alpha transactivation cascade regulates gene activity and chromatin structure of the human serine protease inhibitor gene cluster at 14q32. 1. Proc Natl Acad Sci USA 1999; 96:10308-10313.
314. Monaghan AP, Kaestner KH, Grau E, Schutz G. Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. Development 1993; 119:567-578.
315. Runge D, Runge DM, Drenning SD, Bowen WC Jr, Grandis JR, Michalopoulos GK. Growth and differentiation of rat hepatocytes: changes in transcription factors HNF-3, HNF-4, STAT-3, and STAT-5. Biochem Biophys Res Commun 1998; 250:762-768.
316. Timchenko NA, Wilde M, Darlington GJ. C/EBPalpha regulates formation of S-phasespecific E2F-p107 complexes in livers of newborn mice. Mol Cell Biol 1999; 19:2936-2945.
317. Eferl R, Sibilia M, Hilberg F, Fuchsbichler A, Kufferath I, Guertl B, Zenz R, Wagner EF, Zatloukal K. Functions of c-Jun in liver and heart development. J Cell Biol 1999; 145:1049-1061.
318. Hilberg F, Aguzzi A, Howells N, Wagner EF. c-jun is essential for normal mouse development and hepatogenesis. Nature 1993; 365:179-181.
319. Terada T, Ashida K, Kitamura Y, Matsunaga Y, Takashima K, Kato M, Ohta T. Expression of epithelial-cadherin, alpha-catenin and beta-catenin during human intrahepatic bile duct development: a possible role in bile duct morphogenesis. J Hepatol 1995; 28:263-269.
320. Germain L, Goyette R, Marceau N. Differential cytokeratin and alpha-fetoprotein expression in morphologically distinct epithelial cells emerging at the early stage of rat hepatocarcinogenesis. Cancer Res 1985; 45:673-681.
321. Reid LM, Agelli M. Compositions comprising hepatocyte precursors. U.S. Patent number 5,789,246, 1996.
322. Eghbali B, Kessler JA, Reid LM, Roy C, Spray DC. Involvement of gap junctions in tumorigenesis: transfection of tumor cells with connexin 32 cDNA retards growth in vivo. Proc Natl Acad Sci USA 1991; 88:10701-10705.
323. Yin M, Bradford BU, Wheeler MD, Uesugi T, Froh M, Goyert SM, Thurman RG. Reduced early alcohol-induced liver injury in cd14-deficient mice. J Immunol 2001; 166:4737-4742.
324. MacDonald J, Xu A, Kubota H, LeCluyse E, Hamilton G, Liu H, Rong Y, Moss N, Lodestro C, Luntz T, Wolfe S, Reid L. Liver Cell Culture and Lineage Biology. In: Atala A, Lanza R, eds. Methods of Tissue Engineering. San Diego: Academic Press, 2001:151-201.
325. Langer R, Vacanti JP. Tissue engineering. Science 1993; 260:920-926.
326. Mikos AG, Thorsen AJ, Czerwonka LA, Bao Y, Langer R. Preparation and characterization of poly (L-lactic acid) foam. Polymer 1994; 35:1068-1077.
327. Kwong A, Byrn R, Reid L. Composition and Methods useful for HCV Infection. U.S. Patent Application number PCT/US02/09685, 2001.
328. Gebhardt R. Heterogeneous intrahepatic distribution of glutamine synthetase. Acta Histochem Suppl 1990; 40:23-28.
329. Gebhardt R. Metabolic zonation of the liver: regulation and implications for liver function. Pharmacol Ther 1992; 53:275-354.