Liver ‘organ on a chip’

Experimental Cell Research

Volumn 363, Issue 1, 2018, Pages 15-25

  Beckwitt, Colin H ^a,b,d   Clark, Amanda M ^a   Wheeler, Sarah ^a   Taylor, D Lansing ^a,b,c   Stolz, Donna B ^a,b   Griffith, Linda ^e   Wells, Alan ^a,b,d  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b MCGOWAN INSTITUTE FOR REGENERATIVE MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e Massachusetts Institute of Technology   (United States)

Author keywords

3D culture systems; Microphysiologic systems; Organoids

Indexed keywords

EMBRYONIC STEM CELL; ENDOTHELIUM CELL; HUMAN; INDUCED PLURIPOTENT STEM CELL; KUPFFER CELL; LIVER CELL; LIVER CELL CULTURE; LIVER CELL LINE; NON PARENCHYMAL CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; STELLATE CELL; ANIMAL; BIOLOGICAL MODEL; CYTOLOGY; LAB ON A CHIP; LIVER; MICROFLUIDICS; TISSUE ENGINEERING;

ANIMALS; HEPATOCYTES; HUMANS; LAB-ON-A-CHIP DEVICES; LIVER; MICROFLUIDICS; MODELS, BIOLOGICAL; TISSUE ENGINEERING;

EID: 85039785618     PISSN: 00144827     EISSN: 10902422     Source Type: Journal    
DOI: 10.1016/j.yexcr.2017.12.023     Document Type: Review

References (159)

1. Bhatia, S., Toner, M., Foy, B., Rotem, A., Zonal liver cell heterogeneity: effects of oxygen on metabolic functions of hepatocytes. Cell Eng. 1 (1996), 125–135.
2. Wheeler, S.E., et al. All-human microphysical model of metastasis therapy. Stem Cell Res. Ther., 4(Suppl. 1), 2013, S11.
3. Hakkola, J., Tanaka, E., Pelkonen, O., Developmental expression of cytochrome P450 enzymes in human liver. Pharmacol. Toxicol. 82 (1998), 209–217.
4. Ginsberg, G., et al. Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol. Sci. 66 (2002), 185–200.
5. Blanco, J.G., Harrison, P.L., Evans, W.E., Relling, M.V., Human cytochrome P450 maximal activities in pediatric versus adult liver. Drug Metab. Dispos. 28 (2000), 379–382.
6. Jungermann, K., Kietzmann, T., Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology 31 (2000), 255–260.
7. Buck, L.D., Inman, S.W., Rusyn, I., Griffith, L.G., Co-regulation of primary mouse hepatocyte viability and function by oxygen and matrix. Biotechnol. Bioeng. 111 (2014), 1018–1027.
8. Lee-Montiel, F.T., et al. Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems. Exp. Biol. Med. 242 (2017), 1617–1632.
9. Rodighiero, V., Effects of liver disease on pharmacokinetics. An update. Clin. Pharmacokinet. 37 (1999), 399–431.
10. Taniguchi, H., Masuyama, M., Koyama, H., Oguro, A., Takahashi, T., Quantitative measurement of human tissue hepatic blood volume by C15O inhalation with positron-emission tomography. Liver 16 (1996), 258–262.
11. Lodish, Harvey, Berk, Arnold, Zipursky, S. Lawrence, Matsudaira, Paul, Baltimore, David, J.D., Molecular Cell Biology, 4th edition, 2000, W. H. Freeman.
12. Taylor, D.P., Clark, A., Wheeler, S., Wells, A., Hepatic nonparenchymal cells drive metastatic breast cancer outgrowth and partial epithelial to mesenchymal transition. Breast Cancer Res. Treat. 144 (2014), 551–560.
13. Mathur, A., et al. Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development. Stem Cell Res. Ther., 4(Suppl. 1), 2013, S14.
14. J.J. Lemasters, Liver: Biology and Pathobiology, Biol. Pathobiol., 2001, pp. 257–279. (at) 〈 http://www.gastrohep.org/theliver/18ARIAS018.pdf〉.
15. Hautekeete, M.L., Geerts, A., The hepatic stellate (Ito) cell: its role in human liver disease. Virchows Arch. 430 (1997), 195–207.
16. Thomas, R.J., et al. The effect of three-dimensional co-culture of hepatocytes and hepatic stellate cells on key hepatocyte functions in vitro. Cells Tissues Organs 181 (2005), 67–79.
17. DeLeve, L.D., Liver sinusoidal endothelial cells and liver regeneration. J. Clin. Invest. 123 (2013), 1861–1866.
18. R. Zuber, E. Anzenbacherová P. Anzenbacher Cytochromes P450 and Experimental Models of Drug Metabolism, J. Cell. Mol. Med., vol. 6, pp. 189–198.
19. Baillie, T.A., Rettie, A.E., Role of biotransformation in drug-induced toxicity: influence of intra- and inter-species differences in drug metabolism. Drug Metab. Pharmacokinet. 26 (2011), 15–29.
20. Bale, S.S., et al. In vitro platforms for evaluating liver toxicity. Exp. Biol. Med., 2014, 10.1177/1535370214531872 (1535370214531872).
21. Bhushan, A., et al. Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans. Stem Cell Res. Ther., 4(Suppl. 1), 2013, S16.
22. Vunjak-Novakovic, G., Bhatia, S., Chen, C., Hirschi, K., HeLiVa platform: integrated heart-liver-vascular systems for drug testing in human health and disease. Stem Cell Res. Ther., 4(Suppl. 1), 2013, S8.
23. Khetani, S.R., et al. Microengineered liver tissues for drug testing. J. Lab. Autom., 2015, 10.1177/2211068214566939.
24. Pichard, L., et al. Cyclosporin A drug interactions. screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab. Dispos. 18 (1990), 595–606.
25. LeCluyse, E.L., et al. Isolation and culture of primary human hepatocytes. Methods Mol. Biol. 290 (2005), 207–229.
26. Du, Y., et al. Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming. Cell Stem Cell 14 (2014), 394–403.
27. Bhogal, R.H., et al. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience. PLoS One 6 (2011), 1–8.
28. Alexandre, E., et al. Cryopreservation of adult human hepatocytes obtained from resected liver biopsies. Cryobiology 44 (2002), 103–113.
29. Richert, L., et al. Tissue collection, transport and isolation procedures required to optimize human hepatocyte isolation from waste liver surgical resections. A multilaboratory study. Liver Int. 24 (2004), 371–378.
30. Vondran, F.W.R., et al. Isolation of primary human hepatocytes after partial hepatectomy: criteria for identification of the most promising liver specimen. Artif. Organs 32 (2008), 205–213.
31. Alexandre, E., et al. Cryopreservation of adult human hepatocytes obtained from resected liver biopsies. Cryobiology 44 (2002), 103–113.
32. Donato, M., Lahoz, a., Jimenez, N., Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab. 34 (2006), 1556–1562.
33. Lloyd, T.D.R., et al. Effect of patient, operative and isolation factors on subsequent yield and viability of human hepatocytes for research use. Cell Tissue Bank. 5 (2004), 81–87.
34. Kawahara, T., et al. Factors affecting hepatocyte isolation, engraftment, and replication in an in vivo model. Liver Transpl. 16 (2010), 974–982.
35. Hewes, J.C., et al. A prospective study of isolated human hepatocyte function following liver resection for colorectal liver metastases: the effects of prior exposure to chemotherapy. J. Hepatol. 45 (2006), 263–270.
36. Mcginnity, D.F., Soars, M.G., Urbanowicz, R.A., Riley, R.J., Evaluation of fresh and cryopreserved hepatocytes As in vitro drug metabolism tools for the prediction of metabolic clearance abstract. Drug Metab. Dispos. 32 (2004), 1247–1253.
37. Li, A.P., Human hepatocytes: isolation, cryopreservation and applications in drug development. Chem. Biol. Interact. 168 (2007), 16–29.
38. Sudo, M., Nishihara, M., Takahashi, J., Asahi, S., Long-term stability of cryopreserved human hepatocytes: evaluation of phase I and II drug-metabolizing enzyme activities and cyp3a4/5 induction for more than a decade. Drug Metab. Dispos. 45 (2017), 734–736.
39. Terry, C., Hughes, R.D., Mitry, R.R., Lehec, S.C., Dhawan, A., Cryopreservation-induced nonattachment of human hepatocytes: role of adhesion molecules. Cell Transplant. 16 (2007), 639–647.
40. Lundquist, P., et al. The impact of solute carrier (SLC) drug uptake transporter loss in human and rat cryopreserved hepatocytes on clearance predictions. Drug Metab. Dispos. 42 (2014), 469–480.
41. Roymans, D., et al. Determination of cytochrome P450 1A2 and cytochrome P450 3A4 induction in cryopreserved human hepatocytes. Biochem. Pharmacol. 67 (2004), 427–437.
42. Brown, H.S., Griffin, M., Houston, J.B., Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug Metab. Dispos. 35 (2007), 293–301.
43. Bi, Y.A., Kazolias, D., Duignan, D.B., Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab. Dispos. 34 (2006), 1658–1665.
44. Parkinson, A., Mudra, D.R., Johnson, C., Dwyer, A., Carroll, K.M., The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol. Appl. Pharmacol. 199 (2004), 193–209.
45. Harrill, A.H., et al. Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res. 19 (2009), 1507–1515.
46. Lin, J.H., et al. Species differences in the pharmacokinetics and metabolism of indinavir, a potent human immunodeficiency virus protease inhibitor. Drug Metab. Dispos. 24 (1996), 1111–1120.
47. Pearce, R., Greenway, D., Parkinson, A., Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: Effects on coumarin, dicumarol, and testosterone oxidation. Arch. Biochem. Biophys. 298 (1992), 211–225.
48. Lu, C., Li, A.P., Species comparison in P450 induction: effects of dexamethasone, omeprazole, and rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man, Sprague-Dawley rat, minipig, and beagle dog. Chem. Biol. Interact. 134 (2001), 271–281.
49. Naritomi, Y., et al. Prediction of human hepatic clearance From in vivo animal experiments and in vitro metabolic studies With liver microsomes From animals and humans abstract. Drug Metab. Dispos. 29 (2001), 1316–1324.
50. Huh, D., Hamilton, G.A., Ingber, D.E., From 3D cell culture to organs-on-chips. Trends Cell Biol. 21 (2011), 745–754.
51. Martignoni, M., Groothuis, G.M.M., de Kanter, R., Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin. Drug Metab. Toxicol. 2 (2006), 875–894.
52. Gerets, H.H.J., et al. Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol. Toxicol. 28 (2012), 69–87.
53. Guo, L., et al. Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes. Drug Metab. Dispos. 39 (2011), 528–538.
54. Wilkening, S., Stahl, F., Bader, A., Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab. Dispos. 31 (2003), 1035–1042.
55. Mills, J.B., Rose, K.A., Sadagopan, N., Sahi, J., de Morais, S.M.F., Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line. J. Pharmacol. Exp. Ther. 309 (2004), 303–309.
56. Zhang, X., Scialis, R.J., Feng, B., Leach, K., Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter. Toxicol. Sci. 134 (2013), 73–82.
57. Guillouzo, A., et al. The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Chem. Biol. Interact. 168 (2007), 66–73.
58. Kotani, N., et al. Expression and transport function of drug uptake transporters in differentiated HepaRG cells. Mol. Pharm. 9 (2012), 3434–3441.
59. Le Vee, M., Noel, G., Jouan, E., Stieger, B., Fardel, O., Polarized expression of drug transporters in differentiated human hepatoma HepaRG cells. Toxicol. Vitr. 27 (2013), 1979–1986.
60. Tomida, T., Okamura, H., Satsukawa, M., Yokoi, T., Konno, Y., Multiparametric assay using HepaRG cells for predicting drug-induced liver injury. Toxicol. Lett. 236 (2015), 16–24.
61. Klein, M., et al. A systematic comparison of the impact of inflammatory signaling on absorption, distribution, metabolism, and excretion gene expression and activity in primary human hepatocytes and HepaRG cells. Drug Metab. Dispos. 43 (2015), 273–283.
62. Reya, T., Morrison, S.J., Clarke, M.F., Weissman, I.L., Stem cells, cancer, and cancer stem cells. Nature 414 (2001), 105–111.
63. Malik, N., Rao, M.S., A review of the methods for human iPSC derivation. Methods Mol. Biol. 997 (2013), 23–33.
64. Li, H.Y., et al. Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells. Biomaterials 32 (2011), 5994–6005.
65. Takayama, K., et al. Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction. Mol. Ther. 20 (2012), 127–137.
66. Duan, Y., et al. Differentiation and enrichment of hepatocyte-like cells from human embryonic stem cells in vitro and in vivo. Stem Cells 25 (2007), 3058–3068.
67. Agarwal, S., Holton, K.L., Lanza, R., Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 26 (2008), 1117–1127.
68. Chistiakov, D.A., Chistiakov, P.A., Strategies to produce hepatocytes and hepatocyte-like cells from pluripotent stem cells. Hepatol. Res. 42 (2012), 111–119.
69. Szkolnicka, D., Zhou, W., Lucendo-Villarin, B., Hay, D.C., Pluripotent stem cell-derived hepatocytes: potential and challenges in pharmacology. Annu. Rev. Pharmacol. Toxicol. 53 (2013), 147–159.
70. Bukong, T.N., Lo, T., Szabo, G., Dolganiuc, A., Novel developmental biology-based protocol of embryonic stem cell differentiation to morphologically sound and functional yet immature hepatocytes. Liver Int. 32 (2012), 732–741.
71. Yi, F., Liu, G.-H., Belmonte, J.C.I., Human induced pluripotent stem cells derived hepatocytes: rising promise for disease modeling, drug development and cell therapy. Protein Cell 3 (2012), 246–250.
72. Schwartz, R.E., Fleming, H.E., Khetani, S.R., Bhatia, S.N., Pluripotent stem cell-derived hepatocyte-like cells. Biotechnol. Adv. 32 (2014), 504–513.
73. Baxter, M., et al. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. J. Hepatol. 62 (2015), 581–589.
74. Ware, B.R., Berger, D.R., Khetani, S.R., Prediction of drug-induced liver injury in micropatterned co-cultures containing iPSC-derived human hepatocytes. Toxicol. Sci. 145 (2015), 252–262.
75. Kim, K., et al. Epigenetic memory in induced pluripotent stem cells. Nature 467 (2010), 285–290.
76. Shan, J., et al. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat. Chem. Biol. 9 (2013), 514–520.
77. Wheeler, S.E., et al. Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system. Br. J. Cancer 111 (2014), 2342–2350.
78. Hasmall, S.C., West, D.A., Olsen, K., Roberts, R.A., Role of hepatic non-parenchymal cells in the response of rat hepatocytes to the peroxisome proliferator nafenopin in vitro. Carcinogenesis 21 (2000), 2159–2165.
79. Riccalton-Banks, L., Bhandari, R., Fry, J., Shakesheff, K.M., A simple method for the simultaneous isolation of stellate cells and hepatocytes from rat liver tissue. Mol. Cell. Biochem. 248 (2003), 97–102.
80. Chang, W., et al. Isolation and culture of hepatic stellate cells from mouse liver. Acta Biochim. Biophys. Sin. 46 (2014), 291–298.
81. Werner, M., et al. All-in-one: advanced preparation of human parenchymal and non-parenchymal liver cells. PLoS One, 10, 2015, e0138655.
82. Damm, G., et al. Human parenchymal and non-parenchymal liver cell isolation, culture and characterization. Hepatol. Int. 7 (2013), 951–958.
83. Pfeiffer, E., et al. Featured article: isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells. Exp. Biol. Med. 240 (2015), 645–656.
84. Kegel, V., et al. Protocol for isolation of primary human hepatocytes and corresponding major populations of non-parenchymal liver cells. J. Vis. Exp., 2016, e53069, 10.3791/53069.
85. Damm, G., et al. Human parenchymal and non-parenchymal liver cell isolation, culture and characterization. Hepatol. Int. 7 (2013), 951–958.
86. Koui, Y., et al. An in vitro human liver model by iPSC-derived parenchymal and non-parenchymal cells. Stem Cell Rep. 9 (2017), 490–498.
87. Krause, P., et al. Hepatocyte-supported serum-free culture of rat liver sinusoidal endothelial cells. J. Hepatol. 32 (2000), 718–726.
88. Nelson, L.J., et al. Acetaminophen cytotoxicity is ameliorated in a human liver organotypic co-culture model. Sci. Rep., 5, 2015, 17455.
89. Hang, T.-C., Lauffenburger, D.A., Griffith, L.G., Stolz, D.B., Lipids promote survival, proliferation, and maintenance of differentiation of rat liver sinusoidal endothelial cells in vitro. AJP Gastrointest. Liver Physiol. 302 (2012), G375–G388.
90. Hwa, A.J., et al. Rat liver sinusoidal endothelial cells survive without exogenous VEGF in 3D perfused co-cultures with hepatocytes. FASEB J. 21 (2007), 2564–2579.
91. Griffith, L.G., Wells, A., Stolz, D.B., Engineering liver. Hepatology 60 (2014), 1426–1434.
92. Leclerc, E., Sakai, Y., Fujii, T., Perfusion culture of fetal human hepatocytes in microfluidic environments. Biochem. Eng. J. 20 (2004), 143–148.
93. Liu, Y., Li, H., Yan, S., Wei, J., Li, X., Hepatocyte cocultures with endothelial cells and fibroblasts on micropatterned fibrous mats to promote liver-specific functions and capillary formation capabilities. Biomacromolecules 15 (2014), 1044–1054.
94. Nelson, L.J., et al. Acetaminophen cytotoxicity is ameliorated in a human liver organotypic co-culture model. Sci. Rep., 5, 2015, 17455.
95. Bodnar, R.J., Yates, C.C., Rodgers, M.E., Du, X., Wells, A., IP-10 induces dissociation of newly formed blood vessels. J. Cell Sci. 122 (2009), 2064–2077.
96. Amin, D.N., Hida, K., Bielenberg, D.R., Klagsbrun, M., Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors. Cancer Res. 66 (2006), 2173–2180.
97. Kang, Y.B.A., Rawat, S., Cirillo, J., Bouchard, M., Noh, H.M., Layered long-term co-culture of hepatocytes and endothelial cells on a transwell membrane: toward engineering the liver sinusoid. Biofabrication, 5, 2013, 45008.
98. Yu-Shih, Chen, Ling-Yi, Ke, Ying-Chen, Huang, Cheng-Hsien, Liu, 3D circulatory perfusion-culture system by using high efficiency proportional cell contact. Proc MicroTAS, 2012, 1018–1020.
99. Taylor, D.P., Clark, A., Wheeler, S., Wells, A., Hepatic nonparenchymal cells drive metastatic breast cancer outgrowth and partial epithelial to mesenchymal transition. Breast Cancer Res. Treat. 144 (2014), 551–560.
100. Kawasaki, T., et al. Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. J. Hepatol. 53 (2010), 648–654.
101. Soto-Gutiérrez, A., et al. Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines. Nat. Protoc. 2 (2007), 347–356.
102. Huebert, R.C., et al. Immortalized liver endothelial cells: a cell culture model for studies of motility and angiogenesis. Lab. Investig. 90 (2010), 1770–1781.
103. Kitani, H., et al. Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse strain. Results Immunol. 4 (2014), 68–74.
104. Melino, M., et al. Macrophage secretory products induce an inflammatory phenotype in hepatocytes. World J. Gastroenterol. 18 (2012), 1732–1744.
105. Matak, P., et al. Activated macrophages induce hepcidin expression in HuH7 hepatoma cells. Haematologica 94 (2009), 773–780.
106. Sarkar, U., et al. Metabolite profiling and pharmacokinetic evaluation of hydrocortisone in a perfused three-dimensional human liver bioreactor. Drug Metab. Dispos. 43 (2015), 1091–1099.
107. Boltjes, A., Movita, D., Boonstra, A., Woltman, A.M., The role of Kupffer cells in hepatitis B and hepatitis C virus infections. J. Hepatol. 61 (2014), 660–671.
108. Yin, C., Evason, K.J., Asahina, K., Stainier, D.Y.R., Hepatic stellate cells in liver development, regeneration, and cancer. J. Clin. Investig. 123 (2013), 1902–1910.
109. De Minicis, S., et al. Gene expression profiles during hepatic stellate cell activation in culture and in vivo. Gastroenterology 132 (2007), 1937–1946.
110. Friedman, S.L., Hepatic stellate cells: protean,protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev. 88 (2008), 125–172.
111. Xu, L., et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 54 (2005), 142–151.
112. Friedman, S.L., Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev. 88 (2008), 125–172.
113. P. Krause, F. Saghatolislam, S. Koenig, K. Unthan-Fechner, I. Probst Maintaining Hepatocyte Differentiation in Vitro through Co-culture with Hepatic Stellate Cells. In Vitro Cell. Dev. Biol. Anim., vol. 45, pp. 205–212.
114. Soldatow, V.Y., LeCluyse, E.L., Griffith, L.G., Rusyn, I., In vitro models for liver toxicity testing. Toxicol. Res. 2 (2013), 23–39.
115. Dunn, J.C.Y., Tompkins, R.G., Yarmush, M.L., Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation. J. Cell Biol. 116 (1992), 1043–1053.
116. Novik, E., Maguire, T.J., Chao, P., Cheng, K.C., Yarmush, M.L., A microfluidic hepatic coculture platform for cell-based drug metabolism studies. Biochem. Pharmacol. 79 (2010), 1036–1044.
117. Godoy, P., et al. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch. Toxicol., 87, 2013.
118. C. Guguen-Guillouzo, A. Guillouzo, in 1–40, 2010. 〈 http://doi.org/10.1007/978-1-60761-688-7_1〉.
119. Khetani, S.R., Bhatia, S.N., Microscale culture of human liver cells for drug development. Nat. Biotechnol. 26 (2008), 120–126.
120. Khetani, S.R., et al. Use of micropatterned cocultures to detect compounds that cause drug-induced liver injury in humans. Toxicol. Sci. 132 (2013), 107–117.
121. Ukairo, O., et al. Long-term stability of primary rat hepatocytes in micropatterned cocultures. J. Biochem. Mol. Toxicol. 27 (2013), 204–212.
122. Chan, T.S., et al. Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. Drug Metab. Dispos. 41 (2013), 2024–2032.
123. Dixit, V., Moore, A., Tsao, H., Hariparsad, N., Application of micropatterned cocultured hepatocytes to evaluate the inductive potential and degradation rate of major xenobiotic metabolizing enzymes. Drug Metab. Dispos. 44 (2016), 250–261.
124. Dixit, V., Moore, A., Tsao, H., Hariparsad, N., Application of micropatterned cocultured hepatocytes to evaluate the inductive potential and degradation rate of major xenobiotic metabolizing enzymes. Drug Metab. Dispos. 44 (2016), 250–261.
125. Cho, C., et al. Layered patterning of hepatocytes in co-culture systems using microfabricated stencils. Biotechniques 48 (2010), 47–52.
126. Zinchenko, Y.S., Culberson, C.R., Coger, R.N., Contribution of non-parenchymal cells to the performance of micropatterned hepatocytes. Tissue Eng., 12, 2006 (2241–1251).
127. Faulk, D.M., Johnson, S.A., Zhang, L., Badylak, S.F., Role of the extracellular matrix in whole organ engineering. J. Cell. Physiol. 229 (2014), 984–989.
128. Skardal, A., et al. Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function. Biomaterials 33 (2012), 4565–4575.
129. Loneker, A.E., Faulk, D.M., Hussey, G.S., D'Amore, A., Badylak, S.F., Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype in-vitro. J. Biomed. Mater. Res. Part A 104 (2016), 957–965.
130. You, J., et al. Characterizing the effects of heparin gel stiffness on function of primary hepatocytes. Tissue Eng. Part A 19 (2013), 2655–2663.
131. Fukuda, J., Sakai, Y., Nakazawa, K., Novel hepatocyte culture system developed using microfabrication and collagen/polyethylene glycol microcontact printing. Biomaterials 27 (2006), 1061–1070.
132. Fukuda, J., et al. Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures. Biomaterials 27 (2006), 5259–5267.
133. Li, C.Y., et al. Micropatterned cell-cell interactions enable functional encapsulation of primary hepatocytes in hydrogel microtissues. Tissue Eng. Part A 0 (2014), 1–13.
134. Bell, C.C., et al. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci. Rep., 6, 2016, 25187.
135. Kostadinova, R., et al. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity. Toxicol. Appl. Pharmacol. 268 (2013), 1–16.
136. Gunness, P., et al. 3D organotypic cultures of human HepaRG cells: a tool for in vitro toxicity studies. Toxicol. Sci. 133 (2013), 67–78.
137. Roy, P., Washizu, J., Tilles, A.W., Yarmush, M.L., Toner, M., Effect of flow on the detoxification function of rat hepatocytes in a bioartificial liver reactor. Cell Transplant. 10 (2001), 609–614.
138. Tostões, R.M., et al. Human liver cell spheroids in extended perfusion bioreactor culture for repeated-dose drug testing. Hepatology 55 (2012), 1227–1236.
139. Park, J., et al. Radial flow hepatocyte bioreactor using stacked microfabricated grooved substrates. Biotechnol. Bioeng. 99 (2008), 455–467.
140. Vinci, B., et al. Modular bioreactor for primary human hepatocyte culture: medium flow stimulates expression and activity of detoxification genes. Biotechnol. J. 6 (2011), 554–564.
141. Clark, A.M., et al. A microphysiological system model of therapy for liver micrometastases. Exp. Biol. Med., 2014, 10.1177/1535370214532596 (1535370214532596).
142. Clark, A.M., et al. A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties. Lab Chip 17 (2017), 156–168.
143. Powers, M.J., et al. A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol. Bioeng. 78 (2002), 257–269.
144. Domansky, K., et al. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10 (2010), 51–58.
145. Sarkar, U., et al. Metabolite profiling and pharmacokinetic evaluation of hydrocortisone in a perfused three-dimensional human liver bioreactor. Drug Metab. Dispos. 43 (2015), 1091–1099.
146. Snouber, L.C., et al. Metabolomics-on-a-chip of hepatotoxicity induced by anticancer drug flutamide and its active metabolite hydroxyflutamide using hepg2/c3a microfluidic biochips. Toxicol. Sci. 132 (2013), 8–20.
147. Choucha-Snouber, L., et al. Investigation of ifosfamide nephrotoxicity induced in a liver-kidney co-culture biochip. Biotechnol. Bioeng. 110 (2013), 597–608.
148. Hoffmann, S.A., et al. Analysis of drug metabolism activities in a miniaturized liver cell bioreactor for use in pharmacological studies. Biotechnol. Bioeng. 109 (2012), 3172–3181.
149. Guengerich, F.P., Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu. Rev. Pharmacol. Toxicol. 39 (1999), 1–17.
150. Zhang, M.Y., et al. Microfluidic environment for high density hepatocyte culture. Biomed. Microdevices 10 (2008), 117–121.
151. Lee, P.J., Hung, P.J., Lee, L.P., An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol. Bioeng. 97 (2007), 1340–1346.
152. Chao, P., Maguire, T., Novik, E., Cheng, K.C., Yarmush, M.L., Evaluation of a microfluidic based cell culture platform with primary human hepatocytes for the prediction of hepatic clearance in human. Biochem. Pharmacol. 78 (2009), 625–632.
153. Vernetti, L.A., et al. A human liver microphysiology platform for investigating physiology, drug safety, and disease models. Exp. Biol. Med. 241 (2016), 101–114.
154. Senutovitch, N., et al. Fluorescent protein biosensors applied to microphysiological systems. Exp. Biol. Med. 240 (2015), 795–808.
155. Soto-Gutierrez, A., Gough, A., Vernetti, L.A., Taylor, D.L., Monga, S.P., Pre-clinical and clinical investigations of metabolic zonation in liver diseases: the potential of microphysiology systems. Exp. Biol. Med. 242 (2017), 1605–1616.
156. Gough, A., Vernetti, L., Bergenthal, L., Shun, T.Y., Taylor, D.L., The Microphysiology systems database for analyzing and modeling compound interactions with human and animal organ models. Appl. Vitr. Toxicol. 2 (2016), 103–117.
157. Vernetti, L., et al. Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Sci. Rep., 7, 2017, 42296.
158. Yu, J., et al. Quantitative systems pharmacology approaches applied to microphysiological systems (MPS): data interpretation and multi-MPSIntegration. CPT Pharmacomet. Syst. Pharmacol. 4 (2015), 585–594.
159. Stern, A.M., Schurdak, M.E., Bahar, I., Berg, J.M., Taylor, D.L., A perspective on implementing a quantitative systems pharmacology platform for drug discovery and the advancement of personalized medicine. J. Biomol. Screen. 21 (2016), 521–534.