Emerging in Vitro Liver Technologies for Drug Metabolism and Inter-Organ Interactions

Tissue Engineering - Part B: Reviews

Volumn 22, Issue 5, 2016, Pages 383-394

  Bale, Shyam Sundhar ^a   Moore, Laura ^a   Yarmush, Martin ^a,b   Jindal, Rohit ^a  

^a SHRINERS HOSPITALS FOR CHILDREN   (United States)

^b RUTGERS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOMOLECULES; CELL CULTURE; DIAGNOSIS; METABOLISM; METABOLITES; PHYSIOLOGY; STEM CELLS; TOXICITY;

DRUG EFFICACY; DRUG METABOLISMS; DRUG SCREENING; HEPATIC CELLS; HEPATOTOXICITY; PRIMARY HEPATOCYTE; STATE OF THE ART; THERAPEUTIC AGENTS;

PHYSIOLOGICAL MODELS;

BIOREACTOR; DRUG METABOLISM; HUMAN; IN VITRO STUDY; INTERCONNECTED MULTIWELL PLATE SYSTEM; LABORATORY DEVICE; LIVER; LIVER CELL; MICROFLUIDIC INTERCONNECTED SYSTEM; MULTIWELL PLATE SYSTEM; NONHUMAN; PRIORITY JOURNAL; REVIEW; STATIC MICROFABRICATED PLATFORM; STEM CELL; TISSUE INTERACTION; ADVERSE DRUG REACTION; PRECLINICAL STUDY;

DRUG EVALUATION, PRECLINICAL; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HEPATOCYTES; HUMANS; LIVER;

EID: 84990817521     PISSN: 19373368     EISSN: 19373376     Source Type: Journal    
DOI: 10.1089/ten.teb.2016.0031     Document Type: Review

References (73)

1. Lee, W.M. Drug-induced hepatotoxicity. N Engl J Med 349, 474, 2003.
2. Schuster, D., Laggner, C., and Langer, T. Why drugs fail - a study on side effects in new chemical entities. Curr Pharm Des 11, 3545, 2005.
3. Ikeda, K., Yoshisue, K., Matsushima, E., Nagayama, S., Kobayashi, K., Tyson, C.A., Chiba, K., and Kawaguchi, Y. Bioactivation of tegafur to 5-fluorouracil is catalyzed by cytochrome P-450 2A6 in human liver microsomes in vitro. Clin Cancer Res 6, 4409, 2000.
4. Longley, D.B., Harkin, D.P., and Johnston, P.G. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3, 330, 2003.
5. Bruggemann, S.K., Kisro, J., and Wagner, T. Ifosfamide cytotoxicity on human tumor and renal cells: role of chloroacetaldehyde in comparison to 4-hydroxyifosfamide. Cancer Res 57, 2676, 1997.
6. Soldatow, V.Y., LeCluyse, E.L., Griffith, L.G., and Rusyn, I. In vitro models for liver toxicity testing. Toxicol Res 2, 23, 2013.
7. Bale, S.S., Vernetti, L., Senutovitch, N., Jindal, R., Hegde, M., Gough, A., McCarty, W.J., Bakan, A., Bhushan, A., Shun, T.Y., Golberg, I., Debiasio, R., Usta, B.O., Taylor, D.L., and Yarmush, M.L. In vitro platforms for evaluating liver toxicity. Exp Biol Med (Maywood) 239, 1180, 2014.
8. Godoy, P., Hewitt, N., Albrecht, U., Andersen, M., Ansari, N., Bhattacharya, S., 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, 1315, 2013.
9. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., Dorato, M., Van Deun, K., Smith, P., Berger, B., and Heller, A. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32, 56, 2000.
10. Greaves, P., Williams, A., and Eve, M. First dose of potential new medicines to humans: how animals help. Nat Rev Drug Discov 3, 226, 2004.
11. Mutlib, A.E., Gerson, R.J., Meunier, P.C., Haley, P.J., Chen, H., Gan, L.S., Davies, M.H., Gemzik, B., Christ, D.D., Krahn, D.F., Markwalder, J.A., Seitz, S.P., Robertson, R.T., and Miwa, G.T. The species-dependent metabolism of efavirenz produces a nephrotoxic glutathione conjugate in rats. Toxicol Appl Pharmacol 169, 102, 2000.
12. Ogburn, E.T., Jones, D.R., Masters, A.R., Xu, C., Guo, Y., and Desta, Z. Efavirenz primary and secondary metabolism in vitro and in vivo: identification of novel metabolic path-ways and cytochrome P450 2A6 as the principal catalyst of efavirenz 7-hydroxylation. Drug Metab Dispos 38, 1218, 2010.
13. Wilkening, S., Stahl, F., and Bader, A. Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab Dispos 31, 1035, 2003.
14. Guo, L., Dial, S., Shi, L., Branham, W., Liu, J., Fang, J.L., Green, B., Deng, H., Kaput, J., and Ning, B. Similarities and differences in the expression of drugmetabolizing enzymes between human hepatic cell lines and primary human hepatocytes. Drug Metab Dispos 39, 528, 2011.
15. Choucha-Snouber, L., Aninat, C., Grsicom, L., Madalinski, G., Brochot, C., Poleni, P.E., Razan, F., Guillouzo, C.G., Legallais, C., Corlu, A., and Leclerc, E. Investigation of ifosfamide nephrotoxicity induced in a liver-kidney coculture biochip. Biotechnol Bioeng 110, 597, 2013.
16. Antherieu, S., Chesne, C., Li, R., Camus, S., Lahoz, A., Picazo, L., Turpeinen, M., Tolonen, A., Uusitalo, J., Guguen-Guillouzo, C., and Guillouzo, A. Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab Dispos 38, 516, 2010.
17. Aninat, C., Piton, A., Glaise, D., Le Charpentier, T., Langouet, S., Morel, F., Guguen-Guillouzo, C., and Guillouzo, A. Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. Drug Metab Dispos 34, 75, 2006.
18. Hart, S.N., Li, Y., Nakamoto, K., Subileau, E.A., Steen, D., and Zhong, X.B. A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues. Drug Metab Dispos 38, 988, 2010.
19. Shan, J., Schwartz, R.E., Ross, N.T., Logan, D.J., Thomas, D., Duncan, S.A., North, T.E., Goessling, W., Carpenter, A.E., and Bhatia, S.N. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 9, 514, 2013.
20. Levy, G., Bomze, D., Heinz, S., Ramachandran, S.D., Noerenberg, A., Cohen, M., Shibolet, O., Sklan, E., Braspenning, J., and Nahmias, Y. Long-term culture and expansion of primary human hepatocytes. Nat Biotechnol 33, 1264, 2015.
21. Duan, Y., Ma, X., Zou, W., Wang, C., Bahbahan, I.S., Ahuja, T.P., Tolstikov, V., and Zern, M.A. Differentiation and characterization of metabolically functioning hepatocytes from human embryonic stem cells. Stem Cells 28, 674, 2010.
22. Ogawa, S., Surapisitchat, J., Virtanen, C., Ogawa, M., Niapour, M., Sugamori, K.S., Wang, S., Tamblyn, L., Guillemette, C., Hoffmann, E., Zhao, B., Strom, S., Laposa, R.R., Tyndale, R.F., Grant, D.M., and Keller, G. Threedimensional culture and cAMP signaling promote the maturation of human pluripotent stem cell-derived hepatocytes. Development 140, 3285, 2013.
23. Si-Tayeb, K., Noto, F.K., Nagaoka, M., Li, J., Battle, M.A., Duris, C., North, P.E., Dalton, S., and Duncan, S.A. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51, 297, 2010.
24. Sullivan, G.J., Hay, D.C., Park, I.H., Fletcher, J., Hannoun, Z., Payne, C.M., Dalgetty, D., Black, J.R., Ross, J.A., Samuel, K., Wang, G., Daley, G.Q., Lee, J.H., Church, G.M., Forbes, S.J., Iredale, J.P., and Wilmut, I. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51, 329, 2010.
25. Du, Y., Wang, J., Jia, J., Song, N., Xiang, C., Xu, J., Hou, Z., Su, X., Liu, B., Jiang, T., Zhao, D., Sun, Y., Shu, J., Guo, Q., Yin, M., Sun, D., Lu, S., Shi, Y., and Deng, H. Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming. Cell Stem Cell 14, 394, 2014.
26. Zhou, S.F., Liu, J.P., and Chowbay, B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 41, 89, 2009.
27. Takayama, K., Morisaki, Y., Kuno, S., Nagamoto, Y., Harada, K., Furukawa, N., Ohtaka, M., Nishimura, K., Imagawa, K., Sakurai, F., Tachibana, M., Sumazaki, R., Noguchi, E., Nakanishi, M., Hirata, K., Kawabata, K., and Mizuguchi, H. Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPSderived hepatocytes. Proc Natl Acad Sci U S A 111, 16772, 2014.
28. Schwartz, R.E., Fleming, H.E., Khetani, S.R., and Bhatia, S.N. Pluripotent stem cell-derived hepatocyte-like cells. Biotechnol Adv 32, 504, 2014.
29. Dunn, J.C., Yarmush, M.L., Koebe, H.G., and Tompkins, R.G. Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB J 3, 174, 1989.
30. Moghe, P.V., Berthiaume, F., Ezzell, R.M., Toner, M., Tompkins, R.G., and Yarmush, M.L. Culture matrix configuration and composition in the maintenance of hepatocyte polarity and function. Biomaterials 17, 373, 1996.
31. Ryan, C.M., Carter, E.A., Jenkins, R.L., Sterling, L.M., Yarmush, M.L., Malt, R.A., and Tompkins, R.G. Isolation and long-term culture of human hepatocytes. Surgery 113, 48, 1993.
32. Lin, K.H., Hino, H., Maeda, S., Inagaki, H., Airat, J.V., and Saito, T. Albumin synthesis by rat hepatocytes cultured on collagen gels is sustained specifically by heparin. Exp Cell Res 219, 717, 1995.
33. Tong, J.Z., Sarrazin, S., Cassio, D., Gauthier, F., and Alvarez, F. Application of spheroid culture to human hepatocytes and maintenance of their differentiation. Biol Cell 81, 77, 1994.
34. Glicklis, R., Shapiro, L., Agbaria, R., Merchuk, J.C., and Cohen, S. Hepatocyte behavior within three-dimensional porous alginate scaffolds. Biotechnol Bioeng 67, 344, 2000.
35. Wang, S., Nagrath, D., Chen, P.C., Berthiaume, F., and Yarmush, M.L. Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide hydrogel. Tissue Eng Part A 14, 227, 2008.
36. Hasirci, V., Berthiaume, F., Bondre, S.P., Gresser, J.D., Trantolo, D.J., Toner, M., and Wise, D.L. Expression of liver-specific functions by rat hepatocytes seeded in treated poly(lactic-co-glycolic) acid biodegradable foams. Tissue Eng 7, 385, 2001.
37. Khetani, S.R., and Bhatia, S.N. Microscale culture of human liver cells for drug development. Nat Biotechnol 26, 120, 2008.
38. Jindal, R., Nahmias, Y., Tilles, A.W., Berthiaume, F., and Yarmush, M.L. Amino acid-mediated heterotypic interaction governs performance of a hepatic tissue model. FASEB J 23, 2288, 2009.
39. Jindal, R., Patel, S.J., and Yarmush, M.L. Tissueengineered model for real-time monitoring of liver inflammation. Tissue Eng Part C Methods 17, 113, 2011.
40. Bale, S.S., Golberg, I., Jindal, R., McCarty, W.J., Luitje, M., Hegde, M., Bhushan, A., Usta, O.B., and Yarmush, M.L. Long-term coculture strategies for primary hepatocytes and liver sinusoidal endothelial cells. Tissue Eng Part C Methods 21, 413, 2015.
41. Kostadinova, R., Boess, F., Applegate, D., Suter, L., Weiser, T., Singer, T., Naughton, B., and Roth, A. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity. Toxicol Appl Pharmacol 268, 1, 2013.
42. Esch, M.B., Prot, J.-M., Wang, Y.I., Miller, P., Llamas-Vidales, J.R., Naughton, B.A., Applegate, D.R., and Shuler, M.L. Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow. Lab Chip 15, 2269, 2015.
43. Milosevic, N., Schawalder, H., and Maier, P. Kupffer cellmediated differential down-regulation of cytochrome P450 metabolism in rat hepatocytes. Eur J Pharmacol 368, 75, 1999.
44. Tilles, A.W., Baskaran, H., Roy, P., Yarmush, M.L., and Toner, M. Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor. Biotechnol Bioeng 73, 379, 2001.
45. Hegde, M., Jindal, R., Bhushan, A., Bale, S.S., McCarty, W.J., Golberg, I., Usta, O.B., and Yarmush, M.L. Dynamic interplay of flow and collagen stabilizes primary hepatocytes culture in a microfluidic platform. Lab Chip 14, 2033, 2014.
46. Bale, S.S., Sridharan, G.V., Golberg, I., Prodanov, L., McCarty, W.J., Usta, O.B., Jindal, R., and Yarmush, M.L. A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity. Technology 03, 155, 2015.
47. Mehling, M., and Tay, S. Microfluidic cell culture. Curr Opin Biotechnol 25, 95, 2014.
48. Lau, Y.Y., Chen, Y.H., Liu, T.T., Li, C., Cui, X., White, R.E., and Cheng, K.C. Evaluation of a novel in vitro Caco-2 hepatocyte hybrid system for predicting in vivo oral bioavailability. Drug Metab Dispos 32, 937, 2004.
49. Li, C., Liu, T., Cui, X., Uss, A.S., and Cheng, K.C. Development of in vitro pharmacokinetic screens using Caco-2, human hepatocyte, and Caco-2/human hepatocyte hybrid systems for the prediction of oral bioavailability in humans. J Biomol Screen 12, 1084, 2007.
50. Li, A.P., Bode, C., and Sakai, Y. A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells. Chem Biol Interact 150, 129, 2004.
51. Li, A.P. The use of the Integrated Discrete Multiple Organ Co-culture (IdMOC) system for the evaluation of multiple organ toxicity. Altern Lab Anim 37, 377, 2009.
52. Li, A.P. Metabolism Comparative Cytotoxicity Assay (MCCA) and Cytotoxic Metabolic Pathway Identification Assay (CMPIA) with cryopreserved human hepatocytes for the evaluation of metabolism-based cytotoxicity in vitro: proof-of-concept study with aflatoxin B1. Chem Biol Interact 179, 4, 2009.
53. Li, A.P., Uzgare, A., and LaForge, Y.S. Definition of metabolism-dependent xenobiotic toxicity with co-cultures of human hepatocytes and mouse 3T3 fibroblasts in the novel integrated discrete multiple organ co-culture (Id-MOC) experimental system: results with model toxicants aflatoxin B1, cyclophosphamide and tamoxifen. Chem Biol Interact 199, 1, 2012.
54. Li, A.P. Evaluation of adverse drug properties with cryopreserved human hepatocytes and the Integrated Discrete Multiple Organ Co-culture (IdMOC(TM)) System. Toxicol Res 31, 137, 2015.
55. Guzzardi, M.A., Vozzi, F., and Ahluwalia, A.D. Study of the crosstalk between hepatocytes and endothelial cells using a novel multicompartmental bioreactor: a comparison between connected cultures and cocultures. Tissue Eng Part A 15, 3635, 2009.
56. Iori, E., Vinci, B., Murphy, E., Marescotti, M.C., Avogaro, A., and Ahluwalia, A. Glucose and fatty acid metabolism in a 3 tissue in-vitro model challenged with normo-and hyperglycaemia. PLoS One 7, e34704, 2012.
57. Ucciferri, N., Sbrana, T., and Ahluwalia, A. Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism. Front Bioeng Biotechnol 2, 74, 2014.
58. van Midwoud, P.M., Merema, M.T., Verpoorte, E., and Groothuis, G.M. A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices. Lab Chip 10, 2778, 2010.
59. Ouattara, D.A., Choi, S.-H., Sakai, Y., Péry, A.R.R., and Brochot, C. Kinetic modelling of in vitro cell-based assays to characterize non-specific bindings and ADME processes in a static and a perfused fluidic system. Toxicol Lett 205, 310, 2011.
60. Viravaidya, K., and Shuler, M.L. Incorporation of 3T3-L1 cells to mimic bioaccumulation in a microscale cell culture analog device for toxicity studies. Biotechnol Prog 20, 590, 2004.
61. Tatosian, D.A., and Shuler, M.L. A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers. Biotechnol Bioeng 103, 187, 2009.
62. Mahler, G.J., Esch, M.B., Glahn, R.P., and Shuler, M.L. Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity. Biotechnol Bioeng 104, 193, 2009.
63. Zhang, C., Zhao, Z., Rahim, N.A.A., Noort, D.v., and Yu, H. Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments. Lab Chip 9, 3185, 2009.
64. Sung, J.H., Kam, C., and Shuler, M.L. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10, 446, 2010.
65. Imura, Y., Yoshimura, E., and Sato, K. Micro total bioassay system for oral drugs: evaluation of gastrointestinal degradation, intestinal absorption, hepatic metabolism, and bioactivity. Anal Sci 28, 197, 2012.
66. Ma, L., Barker, J., Zhou, C., Li, W., Zhang, J., Lin, B., Foltz, G., Kublbeck, J., and Honkakoski, P. Towards personalized medicine with a three-dimensional micro-scale perfusion-based two-chamber tissue model system. Biomaterials 33, 4353, 2012.
67. Wagner, I., Materne, E.-M., Brincker, S., Süßbier, U., Frädrich, C., Busek, M., Sonntag, F., Sakharov, D.A., Trushkin, E.V., Tonevitsky, A.G., Lauster, R., and Marx, U. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab Chip 13, 3538, 2013.
68. Leclerc, E., Hamon, J., and Bois, F.Y. Investigation of ifosfamide and chloroacetaldehyde renal toxicity through integration of in vitro liver-kidney microfluidic data and pharmacokinetic-system biology models. J Appl Toxicol 36, 330, 2016.
69. Sutherland, M.L., Fabre, K.M., and Tagle, D.A. The National Institutes of Health microphysiological systems program focuses on a critical challenge in the drug discovery pipeline. Stem Cell Res Ther 4 Suppl 1, I1, 2013.
70. Fabre, K.M., Livingston, C., and Tagle, D.A. Organs-onchips (microphysiological systems): tools to expedite efficacy and toxicity testing in human tissue. Exp Biol Med (Maywood) 239, 1073, 2014.
71. Wikswo, J.P., Curtis, E.L., Eagleton, Z.E., Evans, B.C., Kole, A., Hofmeister, L.H., and Matloff, W.J. Scaling and systems biology for integrating multiple organs-on-achip. Lab Chip 13, 3496, 2013.
72. Viravaidya, K., Sin, A., and Shuler, M.L. Development of a microscale cell culture analog to probe naphthalene toxicity. Biotechnol Prog 20, 316, 2004.
73. Moraes, C., Labuz, J.M., Leung, B.M., Inoue, M., Chun, T.H., and Takayama, S. On being the right size: scaling effects in designing a human-on-a-chip. IntegrBiol (Camb) 5, 1149, 2013.