1932

Abstract

The liver is the central hub of xenobiotic metabolism and consequently the organ most prone to cosmetic- and drug-induced toxicity. Failure to detect liver toxicity or to assess compound clearance during product development is a major cause of postmarketing product withdrawal, with disastrous clinical and financial consequences. While small animals are still the preferred model in drug development, the recent ban on animal use in the European Union created a pressing need to develop precise and efficient tools to detect human liver toxicity during cosmetic development. This article includes a brief review of liver development, organization, and function and focuses on the state of the art of long-term cell culture, including hepatocyte cell sources, heterotypic cell–cell interactions, oxygen demands, and culture medium formulation. Finally, the article reviews emerging liver-on-chip devices and discusses the advantages and pitfalls of individual designs. The goal of this review is to provide a framework to design liver-on-chip devices and criteria with which to evaluate this emerging technology.

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2019-06-04
2024-06-21
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Literature Cited

  1. 1.
    Zakim D, Boyer T. 1996. Hepatology: A Textbook of Liver Disease Philadelphia: Saunders
    [Google Scholar]
  2. 2.
    Desmet VJ. 2001. Organizational principles. The Liver: Biology and Pathobiology IM Arias 3–15 Philadelphia: Lippincott, Williams & Wilkins
    [Google Scholar]
  3. 3.
    Taub R. 2004. Liver regeneration: from myth to mechanism. Nat. Rev. Mol. Cell Biol. 5:836–47
    [Google Scholar]
  4. 4.
    Mauvoisin D, Wang J, Jouffe C, Martin E, Atger F et al. 2014. Circadian clock–dependent and –independent rhythmic proteomes implement distinct diurnal functions in mouse liver. PNAS 111:167–72
    [Google Scholar]
  5. 5.
    Nedredal GI, Elvevold KH, Ytrebo LM, Olsen R, Revhaug A, Smedsrod B 2003. Liver sinusoidal endothelial cells represent an important blood clearance system in pigs. Comp. Hepatol. 2:1
    [Google Scholar]
  6. 6.
    Willekens FLA, Werre JM, Kruijt JK, Roerdinkholder-Stoelwinder B, Groenen-Döpp YAM et al. 2005. Liver Kupffer cells rapidly remove red blood cell–derived vesicles from the circulation by scavenger receptors. Blood 105:2141–45
    [Google Scholar]
  7. 7.
    Behnia K, Bhatia S, Jastromb N, Balis U, Sullivan S et al. 2000. Xenobiotic metabolism by cultured primary porcine hepatocytes. Tissue Eng 6:467–79
    [Google Scholar]
  8. 8.
    Grattagliano I, Portincasa P, Palmieri VO, Palasciano G 2002. Overview on the mechanisms of drug-induced liver cell death. Ann. Hepatol. 1:162–68
    [Google Scholar]
  9. 9.
    Jennings P, Schwarz M, Landesmann B, Maggioni S, Goumenou M et al. 2014. SEURAT-1 liver gold reference compounds: a mechanism-based review. Arch. Toxicol. 88:2099–133
    [Google Scholar]
  10. 10.
    Casale T, Caciari T, Rosati MV, Biagi M, De Sio S et al. 2013. Liver function in workers exposed of the cosmetics industry. Ann. Ig. 25:519–27
    [Google Scholar]
  11. 11.
    Martignoni M, Groothuis GM, de Kanter R 2006. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin. Drug Metab. Toxicol. 2:875–94
    [Google Scholar]
  12. 12.
    Blais EM, Rawls KD, Dougherty BV, Li ZI, Kolling GL et al. 2017. Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions. Nat. Commun. 8:14250
    [Google Scholar]
  13. 13.
    European Parliament, Council of the European Union 2009. Regulation (EC) no. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. Off. J. Eur. Union 342:59–209
    [Google Scholar]
  14. 14.
    Jung J, Zheng M, Goldfarb M, Zaret KS 1999. Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 284:1998–2003
    [Google Scholar]
  15. 15.
    Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W et al. 1995. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373:699–702
    [Google Scholar]
  16. 16.
    Lemaigre F, Zaret KS. 2004. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr. Opin. Genet. Dev. 14:582–90
    [Google Scholar]
  17. 17.
    Sosa-Pineda B, Wigle JT, Oliver G 2000. Hepatocyte migration during liver development requires Prox1. Nat. Genet. 25:254–55
    [Google Scholar]
  18. 18.
    Matsumoto K, Yoshitomi H, Rossant J, Zaret KS 2001. Liver organogenesis promoted by endothelial cells prior to vascular function. Science 297:559–63
    [Google Scholar]
  19. 19.
    Lammert E, Cleaver O, Melton D 2001. Induction of pancreatic differentiation by signals from blood vessels. Science 294:564–67
    [Google Scholar]
  20. 20.
    McCuskey RS, Ekataksin W, LeBouton AV, Nishida J, McCuskey MK et al. 2003. Hepatic microvascular development in relation to the morphogenesis of hepatocellular plates in neonatal rats. Anat. Rec. A 275:1019–30
    [Google Scholar]
  21. 21.
    Nahmias Y, Kramvis Y, Barbe L, Casali M, Berthiaume F, Yarmush ML 2006. A novel formulation of oxygen-carrying matrix enhances liver-specific function of cultured hepatocytes. FASEB J 20:2531–33
    [Google Scholar]
  22. 22.
    Martinez-Hernandez A, Amenta PS. 1995. The extracellular matrix in hepatic regeneration. FASEB J 9:1401–10
    [Google Scholar]
  23. 23.
    Allen JW, Bhatia SN. 2003. Formation of steady-state oxygen gradients in vitro: application to liver zonation. Biotechnol. Bioeng. 82:253–62
    [Google Scholar]
  24. 24.
    Planas-Paz L, Orsini V, Boulter L, Calabrese D, Pikiolek M et al. 2016. The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size. Nat. Cell Biol. 18:467–79
    [Google Scholar]
  25. 25.
    Haussinger D, Lamers WH, Moorman AF 1992. Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. Enzyme 46:72–93
    [Google Scholar]
  26. 26.
    Jungermann K. 1992. Role of intralobular compartmentation in hepatic metabolism. Diabetes Metab 18:81–86
    [Google Scholar]
  27. 27.
    Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA 1992. Extracellular matrix gradients in the space of Disse: relevance to liver biology. Hepatology 15:1198–203
    [Google Scholar]
  28. 28.
    Bouwens L, Bleser PD, Vanderkerken K, Geerts B, Wisse E 1992. Liver cell heterogeneity: functions of non-parenchymal cells. Enzyme 46:155–68
    [Google Scholar]
  29. 29.
    Braet F, Wisse E. 2002. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review. Comp. Hepatol. 1:1
    [Google Scholar]
  30. 30.
    Morin O, Goulet F, Normand C 1988. Liver sinusoidal endothelial cells: isolation, purification, characterization and interaction with hepatocytes. Revis. Biol. Cel. 15:1–85
    [Google Scholar]
  31. 31.
    Nguyen-Lefebvre AT, Horuzsko A. 2015. Kupffer cell metabolism and function. J. Enzymol. Metab. 1:101
    [Google Scholar]
  32. 32.
    Bellan M, Castello LM, Pirisi M 2018. Candidate biomarkers of liver fibrosis: a concise, pathophysiology-oriented review. J. Clin. Transl. Hepatol. 6:317–25
    [Google Scholar]
  33. 33.
    Gores GJ, Kost LJ, LaRusso NF 1986. The isolated perfused rat liver: conceptual and practical considerations. Hepatology 6:511–17
    [Google Scholar]
  34. 34.
    Lee K, Berthiaume F, Stephanopoulos GN, Yarmush DM, Yarmush ML 2000. Metabolic flux analysis of postburn hepatic hypermetabolism. Metab. Eng. 2:312–27
    [Google Scholar]
  35. 35.
    Tavill AS, East AG, Black EG, Nadkarni D, Hoffenberg E 1972. Regulatory factors in the synthesis of plasma proteins by the isolated perfused rat liver. Ciba Found. Symp. 9:155–79
    [Google Scholar]
  36. 36.
    Palmen NG, Evelo CT, Borm PJ, Henderson PT 1993. Toxicokinetics of dimethylacetamide (DMAc) in rat isolated perfused liver. Hum. Exp. Toxicol. 12:127–33
    [Google Scholar]
  37. 37.
    McKindley DS, Chichester C, Raymond R 1999. Effect of endotoxin shock on the clearance of lidocaine and indocyanine green in the perfused rat liver. Shock 12:468–72
    [Google Scholar]
  38. 38.
    Gordon AH, Humphrey JH. 1960. Methods for measuring rates of synthesis of albumin by the isolated perfused rat liver. Biochem. J. 75:240–47
    [Google Scholar]
  39. 39.
    Burke WT. 1960. Urea synthesis in the isolated perfused rat liver. Biochem. Biophys. Res. Commun. 3:525–30
    [Google Scholar]
  40. 40.
    Zhao P, Kalhorn TF, Slattery JT 2002. Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. Hepatology 36:326–35
    [Google Scholar]
  41. 41.
    Martin H, Sarsat JP, Lerche-Langrand C, Housset C, Balladur P et al. 2002. Morphological and biochemical integrity of human liver slices in long-term culture: effects of oxygen tension. Cell Biol. Toxicol. 18:73–85
    [Google Scholar]
  42. 42.
    Fisher RL, Ulreich JB, Nakazato PZ, Brendel K 2001. Histological and biochemical evaluation of precision-cut liver slices. Toxicol. Methods 11:59–79
    [Google Scholar]
  43. 43.
    Lerche-Langrand C, Toutain HJ. 2000. Precision-cut liver slices: characteristics and use for in vitro pharmaco-toxicology. Toxicology 153:221–53
    [Google Scholar]
  44. 44.
    van Midwoud PM, Merema MT, Verpoorte E, Groothuis GMM 2011. Microfluidics enables small-scale tissue-based drug metabolism studies with scarce human tissue. J. Assoc. Lab. Autom. 16:468–76
    [Google Scholar]
  45. 45.
    Schumacher K, Khong Y-M, Chang S, Ni J, Sun W, Yu H 2007. Perfusion culture improves the maintenance of cultured liver tissue slices. Tissue Eng 13:197–205
    [Google Scholar]
  46. 46.
    Norona LM, Nguyen DG, Gerber DA, Presnell SC, LeCluyse EL 2016. Editor's highlight: Modeling compound-induced fibrogenesis in vitro using three-dimensional bioprinted human liver tissues. Toxicol. Sci. 154:354–67
    [Google Scholar]
  47. 47.
    Nguyen DG, Funk J, Robbins JB, Crogan-Grundy C, Presnell SC et al. 2016. Bioprinted 3D primary liver tissues allow assessment of organ-level response to clinical drug induced toxicity in vitro. PLOS ONE 11:e0158674
    [Google Scholar]
  48. 48.
    Ma X, Qu X, Zhu W, Li Y-S, Yuan S et al. 2016. Deterministically patterned biomimetic human iPSC–derived hepatic model via rapid 3D bioprinting. PNAS 113:2206–11
    [Google Scholar]
  49. 49.
    Seglen PO. 1976. Preparation of isolated rat liver cells. Methods Cell Biol 13:29–83
    [Google Scholar]
  50. 50.
    Strain AJ. 1994. Isolated hepatocytes: use in experimental and clinical hepatology. Gut 35:433–36
    [Google Scholar]
  51. 51.
    Kidambi S, Yarmush R, Novik E, Chao PB, Yarmush ML, Nahmias Y 2009. Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance. PNAS 106:15714–19
    [Google Scholar]
  52. 52.
    Azuma H, Paulk N, Ranade A, Dorrell C, Al-Dhalimy M et al. 2007. Robust expansion of human hepatocytes in Fah−/−/Rag2−/−/Il2rg−/− mice. Nat. Biotechnol. 25:903–10
    [Google Scholar]
  53. 53.
    Yarmush ML, Toner M, Dunn JC, Rotem A, Hubel A, Tompkins RG 1992. Hepatic tissue engineering. Development of critical technologies. Ann. N. Y. Acad. Sci. 665:238–52
    [Google Scholar]
  54. 54.
    Hamilton GA, Westmorel C, George AE 2001. Effects of medium composition on the morphology and function of rat hepatocytes cultured as spheroids and monolayers. In Vitro Cell Dev. Biol. Anim. 37:656–67
    [Google Scholar]
  55. 55.
    Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D et al. 2002. Infection of a human hepatoma cell line by hepatitis B virus. PNAS 99:15655–60
    [Google Scholar]
  56. 56.
    Anthérieu S, Chesné C, Li R, Camus S, Lahoz A et al. 2010. Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab. Dispos. 38:516–25
    [Google Scholar]
  57. 57.
    Levy G, Bomze D, Heinz S, Ramachandran SD, Noerenberg A et al. 2015. Long-term culture and expansion of primary human hepatocytes. Nat. Biotechnol. 33:1264–71
    [Google Scholar]
  58. 58.
    Avior Y, Levy G, Zimerman M, Kitsberg D, Schwartz R et al. 2015. Microbial-derived lithocholic acid and vitamin K2 drive the metabolic maturation of pluripotent stem cells–derived and fetal hepatocytes. Hepatology 62:265–78
    [Google Scholar]
  59. 59.
    Cameron K, Tan R, Schmidt-Heck W, Campos G, Lyall Marcus J et al. 2016. Recombinant laminins drive the differentiation and self-organization of hESC-derived hepatocytes. Stem Cell Rep 5:1250–62
    [Google Scholar]
  60. 60.
    Dunn JC, Tompkins RG, Yarmush ML 1991. Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol. Prog. 7:237–45
    [Google Scholar]
  61. 61.
    Dunn JC, Tompkins RG, Yarmush ML 1992. Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation. J. Cell Biol. 116:1043–53
    [Google Scholar]
  62. 62.
    Dunn JC, Yarmush ML, Koebe HG, Tompkins RG 1989. Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB J 3:174–77
    [Google Scholar]
  63. 63.
    Berthiaume F, Moghe PV, Toner M, Yarmush ML 1996. Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: hepatocytes cultured in a sandwich configuration. FASEB J 10:1471–84
    [Google Scholar]
  64. 64.
    Moghe PV, Berthiaume F, Ezzell RM, Toner M, Tompkins RG, Yarmush ML 1996. Culture matrix configuration and composition in the maintenance of hepatocyte polarity and function. Biomaterials 17:373–85
    [Google Scholar]
  65. 65.
    Moghe PV, Coger RN, Toner M, Yarmush ML 1997. Cell–cell interactions are essential for maintenance of hepatocyte function in collagen gel but not on Matrigel. Biotechnol. Bioeng. 56:706–11
    [Google Scholar]
  66. 66.
    Schuetz EG, Li D, Omiecinski CJ, Muller-Eberhard U, Kleinman HK et al. 1988. Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. J. Cell Physiol. 134:309–23
    [Google Scholar]
  67. 67.
    Koide N, Shinji T, Tanabe T, Asano K, Kawaguchi M et al. 1989. Continued high albumin production by multicellular spheroids of adult rat hepatocytes formed in the presence of liver-derived proteoglycans. Biochem. Biophys. Res. Commun. 161:385–91
    [Google Scholar]
  68. 68.
    Peshwa MV, Wu FJ, Sharp HL, Cerra FB, Hu W-S 1996. Mechanistics of formation and ultrastructural evaluation of hepatocyte spheroids. In Vitro Cell. Dev. Biol. Anim. 32:197–203
    [Google Scholar]
  69. 69.
    Abu-Absi SF, Friend JR, Hansen LK, Hu W-S 2002. Structural polarity and functional bile canaliculi in rat hepatocyte spheroids. Exp. Cell Res. 274:56–67
    [Google Scholar]
  70. 70.
    Wu FJ, Friend JR, Remmel RP, Cerra FB, Hu W-S 1999. Enhanced cytochrome P450 IA1 activity of self-assembled rat hepatocyte spheroids. Cell Transplant 8:233–46
    [Google Scholar]
  71. 71.
    Landry J, Bernier D, Ouellet C, Goyette R, Marceau N 1985. Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. J. Cell Biol. 101:914–23
    [Google Scholar]
  72. 72.
    Messner S, Agarkova I, Moritz W, Kelm JM 2013. Multi–cell type human liver microtissues for hepatotoxicity testing. Arch. Toxicol. 87:209–13
    [Google Scholar]
  73. 73.
    Nahmias Y, Schwartz RE, Wei-Shou H, Verfaillie CM, Odde DJ 2006. Endothelium-mediated hepatocyte recruitment in the establishment of liver-like tissue in vitro. Tissue Eng 12:1627–38
    [Google Scholar]
  74. 74.
    Neyrinck A, Eeckhoudt SL, Meunier CJ, Pampfer S, Taper HS et al. 1999. Modulation of paracetamol metabolism by Kupffer cells: a study on rat liver slices. Life Sci 65:2851–59
    [Google Scholar]
  75. 75.
    Jaeschke H, Farhood A. 1991. Neutrophil and Kupffer cell–induced oxidant stress and ischemia–reperfusion injury in rat liver. Am. J. Physiol. Gastrointest. Liver Physiol. 260:G355–62
    [Google Scholar]
  76. 76.
    James LP, Mayeux PR, Hinson JA 2003. Acetaminophen-induced hepatotoxicity. Drug Metab. Dispos. 31:1499–506
    [Google Scholar]
  77. 77.
    Hoebe KH, Witkamp RF, Fink-Gremmels J, Miert ASV, Monshouwer M 2001. Direct cell-to-cell contact between Kupffer cells and hepatocytes augments endotoxin-induced hepatic injury. Am. J. Physiol. Gastrointest. Liver Physiol. 280:G720–28
    [Google Scholar]
  78. 78.
    Milosevic N, Schawalder H, Maier P 1999. Kupffer cell–mediated differential down-regulation of cytochrome P450 metabolism in rat hepatocytes. Eur. J. Pharmacol. 368:75–87
    [Google Scholar]
  79. 79.
    Nguyen TV, Ukairo O, Khetani SR, McVay M, Kanchagar C et al. 2015. Establishment of a hepatocyte–Kupffer cell coculture model for assessment of proinflammatory cytokine effects on metabolizing enzymes and drug transporters. Drug Metab. Dispos. 43:774–85
    [Google Scholar]
  80. 80.
    Leite SB, Roosens T, El Taghdouini A, Mannaerts I, Smout AJ et al. 2016. Novel human hepatic organoid model enables testing of drug-induced liver fibrosis in vitro. Biomaterials 78:1–10
    [Google Scholar]
  81. 81.
    Coll M, Perea L, Boon R, Leite SB, Vallverdu J et al. 2018. Generation of hepatic stellate cells from human pluripotent stem cells enables in vitro modeling of liver fibrosis. Cell Stem Cell 23:101–13
    [Google Scholar]
  82. 82.
    Bhatia SN, Balis UJ, Yarmush ML, Toner M 1999. Effect of cell–cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J 13:1883–900
    [Google Scholar]
  83. 83.
    Khetani SR, Szulgit G, Rio JAD, Barlow C, Bhatia SN 2004. Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling. Hepatology 40:545–54
    [Google Scholar]
  84. 84.
    Cho CH, Berthiaume F, Tilles AW, Yarmush ML 2008. A new technique for primary hepatocyte expansion in vitro. Biotechnol. Bioeng. 101:345–56
    [Google Scholar]
  85. 85.
    Shan J, Schwartz RE, Ross NT, Logan DJ, Thomas D et al. 2013. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat. Chem. Biol. 9:514–20
    [Google Scholar]
  86. 86.
    Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush ML 2006. Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes. Hepatology 43:257–65
    [Google Scholar]
  87. 87.
    Morin O, Normand C. 1986. Long-term maintenance of hepatocyte functional activity in co-culture: requirements for sinusoidal endothelial cells and dexamethasone. J. Cell. Physiol. 129:103–10
    [Google Scholar]
  88. 88.
    Goulet F, Normand C, Morin O 1988. Cellular interactions promote tissue-specific function, biomatrix deposition and junctional communication of primary cultured hepatocytes. Hepatology 8:1010–18
    [Google Scholar]
  89. 89.
    LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH et al. 2003. Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 299:890–93
    [Google Scholar]
  90. 90.
    Nahmias YK, Odde DJ. 2002. Analysis of radiation forces in laser trapping and laser-guided direct writing applications. IEEE J. Quantum Electron. 38:131–41
    [Google Scholar]
  91. 91.
    Nahmias YK, Gao BZ, Odde DJ 2004. Dimensionless parameters for the design of optical traps and laser guidance systems. Appl. Opt. 43:3999–4006
    [Google Scholar]
  92. 92.
    Nahmias Y, Schwartz RE, Verfaillie CM, Odde DJ 2005. Laser-guided direct writing for three-dimensional tissue engineering. Biotechnol. Bioeng. 92:129–36
    [Google Scholar]
  93. 93.
    Yamamoto H, Takada T, Yamanashi Y, Ogura M, Masuo Y et al. 2017. VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body. Sci. Rep. 7:633
    [Google Scholar]
  94. 94.
    Simon N, Dailly E, Combes O, Malaurie E, Lemaire M et al. 1998. Role of lipoproteins in the plasma binding of SDZ PSC 833, a novel multidrug resistance–reversing cyclosporin. Br. J. Clin. Pharmacol. 45:173–75
    [Google Scholar]
  95. 95.
    Tilles AW, Baskaran H, Roy P, Yarmush ML, Toner M 2001. Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor. Biotechnol. Bioeng. 73:379–89
    [Google Scholar]
  96. 96.
    Balis UJ, Behnia K, Dwarakanath B, Bhatia SN, Sullivan SJ et al. 1999. Oxygen consumption characteristics of porcine hepatocytes. Metab. Eng. 1:49–62
    [Google Scholar]
  97. 97.
    Foy BD, Rotem A, Toner M, Tompkins RG, Yarmush ML 1994. A device to measure the oxygen uptake rate of attached cells: importance in bioartificial organ design. Cell Transplant 3:515–27
    [Google Scholar]
  98. 98.
    Lemasters JJ. 2001. Hypoxic, ischemic, and reperfusion injury to liver. The Liver: Biology and Pathobiology IM Arias 257–79 Philadelphia: Lippincott, Williams & Wilkins
    [Google Scholar]
  99. 99.
    Yarmush ML, Toner M, Dunn JCY, Rotem A, Hubel A, Tompkins RG 1992. Hepatic tissue engineering: development of critical technologies. Ann. N. Y. Acad. Sci. 665:238–52
    [Google Scholar]
  100. 100.
    Khetani SR, Bhatia SN. 2007. Microscale culture of human liver cells for drug development. Nat. Biotechnol. 26:120–26
    [Google Scholar]
  101. 101.
    Rotem A, Toner M, Bhatia S, Foy BD, Tompkins RG, Yarmush ML 1994. Oxygen is a factor determining in vitro tissue assembly: effects on attachment and spreading of hepatocytes. Biotechnol. Bioeng. 43:654–60
    [Google Scholar]
  102. 102.
    Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush ML 2006. A novel formulation of oxygen-carrying matrix enhances liver specific function of cultured hepatocytes. FASEB J 20:2531–53
    [Google Scholar]
  103. 103.
    King AT, Mulligan BJ, Lowe KC 1989. Perfluorochemicals and cell culture. Nat. Biotechnol. 7:1037–42
    [Google Scholar]
  104. 104.
    Gordon JE, Dare MR, Palmer AF 2005. Engineering select physical properties of cross-linked red blood cells and a simple a priori estimation of their efficacy as an oxygen delivery vehicle within the context of a hepatic hollow fiber bioreactor. Biotechnol. Prog. 21:1700–7
    [Google Scholar]
  105. 105.
    Rappaport C, Rensch Y, Abbasi M, Kempe M, Rocaboy C et al. 2002. New perfluorocarbon system for multilayer growth of anchorage-dependent mammalian cells. Biotechniques 32:142–51
    [Google Scholar]
  106. 106.
    Williams GM, Bermudez E, Scaramuzzino D 1977. Rat hepatocyte primary cell cultures. III. Improved dissociation and attachment techniques and the enhancement of survival by culture medium. In Vitro 13:809–17
    [Google Scholar]
  107. 107.
    Zupke CA, Stefanovich P, Berthiaume F, Yarmush ML 1998. Metabolic effects of stress mediators on cultured hepatocytes. Biotechnol. Bioeng. 58:222–30
    [Google Scholar]
  108. 108.
    Matthew HWT, Sternberg J, Stefanovich P, Morgan JR, Toner M et al. 1996. Effects of plasma exposure on cultured hepatocytes: implications for bioartificial liver support. Biotechnol. Bioeng. 51:100–11
    [Google Scholar]
  109. 109.
    Chan C, Berthiaume F, Washizu J, Toner M, Yarmush ML 2002. Metabolic pre-conditioning of cultured cells in physiological levels of insulin: generating resistance to the lipid-accumulating effects of plasma in hepatocytes. Biotechnol. Bioeng. 78:753–60
    [Google Scholar]
  110. 110.
    Andersson H, van den Berg A. 2004. Microfabrication and microfluidics for tissue engineering: state of the art and future opportunities. Lab Chip 4:98–103
    [Google Scholar]
  111. 111.
    Park J, Berthiaume F, Toner M, Yarmush ML, Tilles AW 2005. Microfabricated grooved substrates as platforms for bioartificial liver reactors. Biotechnol. Bioeng. 90:632–44
    [Google Scholar]
  112. 112.
    Bavli D, Prill S, Ezra E, Levy G, Cohen M et al. 2016. Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction. PNAS 113:E2231–40
    [Google Scholar]
  113. 113.
    Ledezma GA, Folch A, Bhatia SN, Yarmush ML, Toner M 1999. Numerical model of fluid flow and oxygen transport in a radial-flow microchannel containing hepatocytes. J. Biomech. Eng. 121:58–64
    [Google Scholar]
  114. 114.
    Oleaga C, Bernabini C, Smith AST, Srinivasan B, Jackson M et al. 2016. Multi-organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci. Rep. 6:20030
    [Google Scholar]
  115. 115.
    Chen HJ, Miller P, Shuler ML 2018. A pumpless body-on-a-chip model using a primary culture of human intestinal cells and a 3D culture of liver cells. Lab Chip 18:2036–46
    [Google Scholar]
  116. 116.
    Strain AJ, Neuberger JM. 2002. A bioartificial liver—state of the art. Science 295:1005–9
    [Google Scholar]
  117. 117.
    Griffith LG, Naughton G. 2002. Tissue engineering—current challenges and expanding opportunities. Science 295:1009–16
    [Google Scholar]
  118. 118.
    Ohshima N, Yanagi K, Miyoshi H 1997. Packed-bed type reactor to attain high density culture of hepatocytes for use as a bioartificial liver. Artif. Organs 21:1169–76
    [Google Scholar]
  119. 119.
    Murtas S, Capuani G, Dentini M, Manetti C, Masci G et al. 2005. Alginate beads as immobilization matrix for hepatocytes perfused in a bioreactor: a physico-chemical characterization. J. Biomater. Sci. Polym. Ed. 16:829–46
    [Google Scholar]
  120. 120.
    Li AP, Barker G, Beck D, Colburn S, Monsell R, Pellegrin C 1993. Culturing of primary hepatocytes as entrapped aggregates in a packed bed bioreactor: a potential bioartificial liver. In Vitro Cell Dev. Biol. 29:A249–54
    [Google Scholar]
  121. 121.
    Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A et al. 2002. A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol. Bioeng. 78:257–69
    [Google Scholar]
  122. 122.
    Griffith LG, Swartz MA. 2006. Capturing complex 3D tissue physiology in vitro. Nat. Rev. Mol. Cell Biol. 7:211–24
    [Google Scholar]
  123. 123.
    Powers MJ, Janigian DM, Wack KE, Baker CS, Stolz DB, Griffith LG 2002. Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. Tissue Eng 8:499–513
    [Google Scholar]
  124. 124.
    Schepers A, Li C, Chhabra A, Seney BT, Bhatia S 2016. Engineering a perfusable 3D human liver platform from iPS cells. Lab Chip 16:2644–53
    [Google Scholar]
  125. 125.
    Monga SPS, Hout MS, Baun MJ, Micsenyi A, Muller P et al. 2005. Mouse fetal liver cells in artificial capillary beds in three-dimensional four-compartment bioreactors. Am. J. Pathol. 167:1279–92
    [Google Scholar]
  126. 126.
    Gerlach JC, Mutig K, Sauer IM, Schrade P, Efimova E et al. 2003. Use of primary human liver cells originating from discarded grafts in a bioreactor for liver support therapy and the prospects of culturing adult liver stem cells in bioreactors: a morphologic study. Transplantation 76:781–86
    [Google Scholar]
  127. 127.
    Zeilinger K, Schreiter T, Darnell M, Söderdahl T, Lübberstedt M et al. 2011. Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies. Tissue Eng. C 17:549–56
    [Google Scholar]
  128. 128.
    Kidambi S, Yarmush RS, Novik E, Chao P, Yarmush ML, Nahmias Y 2009. Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance. PNAS 106:15714–19
    [Google Scholar]
  129. 129.
    Kang YB, Eo J, Mert S, Yarmush ML, Usta OB 2018. Metabolic patterning on a chip: towards in vitro liver zonation of primary rat and human hepatocytes. Sci. Rep. 8:8951
    [Google Scholar]
  130. 130.
    Guillouzo A, Corlu A, Aninat C, Glaise D, Morel F, Guguen-Guillouzo C 2007. The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Chem. Biol. Interact. 168:66–73
    [Google Scholar]
  131. 131.
    Maschmeyer I, Lorenz AK, Schimek K, Hasenberg T, Ramme AP et al. 2015. A four-organ chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15:2688–99
    [Google Scholar]
  132. 132.
    Bauer S, Wennberg Huldt C, Kanebratt KP, Durieux I, Gunne D et al. 2017. Functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model. Sci. Rep. 7:14620
    [Google Scholar]
  133. 133.
    Domansky K, Inman W, Serdy J, Dash A, Lim MH, Griffith LG 2010. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10:51–58
    [Google Scholar]
  134. 134.
    Long TJ, Cosgrove PA, Dunn RT, Stolz DB, Hamadeh H et al. 2016. Modeling therapeutic antibody–small molecule drug–drug interactions using a three-dimensional perfusable human liver coculture platform. Drug Metab. Dispos. 44:1940–48
    [Google Scholar]
  135. 135.
    Jang M, Neuzil P, Volk T, Manz A, Kleber A 2015. On-chip three-dimensional cell culture in phaseguides improves hepatocyte functions in vitro. Biomicrofluidics 9:034113
    [Google Scholar]
  136. 136.
    Ehrlich A, Tsytkin-Kirschenzweig S, Ioannidis K, Ayyash M, Riu A et al. 2018. Microphysiological flux balance platform unravels the dynamics of drug induced steatosis. Lab Chip 18:2510–22
    [Google Scholar]
  137. 137.
    Prill S, Bavli D, Levy G, Ezra E, Schmälzlin E et al. 2016. Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone. Arch. Toxicol. 90:1181–91
    [Google Scholar]
  138. 138.
    Zhang YS, Aleman J, Shin SR, Kilic T, Kim D et al. 2017. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. PNAS 114:E2293–302
    [Google Scholar]
  139. 139.
    Tsiaoussis J, Newsome PN, Nelson LJ, Hayes PC, Plevris JN 2001. Which hepatocyte will it be? Hepatocyte choice for bioartifical liver support systems. Liver Transplant 7:2–10
    [Google Scholar]
  140. 140.
    Ebrahimkhani MR, Neiman JAS, Raredon MSB, Hughes DJ, Griffith LG 2014. Bioreactor technologies to support liver function in vitro. Adv. Drug Deliv. Rev. 69/70:132–57
    [Google Scholar]
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