Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk

Biotechnology and Bioengineering

Volumn 114, Issue 11, 2017, Pages 2648-2659

  Chen, Wen L K ^a   Edington, Collin ^a   Suter, Emily ^a   Yu, Jiajie ^a   Velazquez, Jeremy J ^a   Velazquez, Jason G ^a   Shockley, Michael ^a   Large, Emma M ^b   Venkataramanan, Raman ^c   Hughes, David J ^b   Stokes, Cynthia L ^d   Trumper, David L ^a   Carrier, Rebecca L ^e   Cirit, Murat ^a   Griffith, Linda G ^a   Lauffenburger, Douglas A ^a  

^a Massachusetts Institute of Technology Cambridge   (United States)

^b Centre for Innovation and Enterprise   (United Kingdom)

^c UNIVERSITY OF PITTSBURGH   (United States)

^d Stokes Consulting   (United States)

^e Northeastern University   (United States)

Author keywords

CXCR3 ligands; gut liver interaction; microphysiological system; organ on a chip; sepsis

Indexed keywords

CROSSTALK; GENE EXPRESSION; LIGANDS; LIVER; METABOLISM; MODULATION;

CYTOKINE RESPONSE; GENE EXPRESSION DATA; GUT-LIVER INTERACTION; INFLAMMATORY RESPONSE; MICROPHYSIOLOGICAL SYSTEM; ORGAN-ON-A-CHIP; PATHOPHYSIOLOGICAL; SEPSIS;

TISSUE;

ALPHA INTERFERON; BETA INTERFERON; CHEMOKINE RECEPTOR CXCR3; CHOLESTEROL 7ALPHA MONOOXYGENASE; FIBROBLAST GROWTH FACTOR 19; GAMMA INTERFERON; TRANSCRIPTOME; CYTOKINE; IMMUNOLOGIC FACTOR;

ARTICLE; BILE ACID METABOLISM; BILE ACID SYNTHESIS; CYTOKINE RELEASE; DENDRITIC CELL; ENTERITIS; GENE EXPRESSION; GOBLET CELL; HEPATITIS; HUMAN; HUMAN CELL; INTESTINE CELL; INTESTINE TISSUE; KUPFFER CELL; LIVER CELL; LIVER TISSUE; MOLECULAR INTERACTION; PHYSIOLOGICAL PROCESS; PROTEIN EXPRESSION; RNA SEQUENCE; UPREGULATION; CACO-2 CELL LINE; CELL COMMUNICATION; CELL CULTURE; COCULTURE; COLON; DEVICE FAILURE ANALYSIS; DEVICES; EQUIPMENT DESIGN; IMMUNOASSAY; IMMUNOLOGY; INFLAMMATION; LAB ON A CHIP; LIVER; MINIATURIZATION; SYSTEM ANALYSIS;

CACO-2 CELLS; CELL COMMUNICATION; CELLS, CULTURED; COCULTURE TECHNIQUES; COLON; CYTOKINES; EQUIPMENT DESIGN; EQUIPMENT FAILURE ANALYSIS; HEPATOCYTES; HUMANS; IMMUNOASSAY; IMMUNOLOGIC FACTORS; INFLAMMATION; KUPFFER CELLS; LAB-ON-A-CHIP DEVICES; LIVER; MINIATURIZATION; SYSTEMS INTEGRATION;

EID: 85026290257     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.26370     Document Type: Article

References (78)

1. Abaci HE, Shuler ML. 2015. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling. Integrative Biology 7(4):383–391.
2. Brown RP, Delp MD, Lindstedt SL, Rhomberg LR, Beliles RP. 1997. Physiological parameter values for physiologically based pharmacokinetic models. Toxicol Ind Health 13(4):407–484.
3. Clark AM, Wheeler SE, Young CL, Stockdale L, Shepard Neiman J, Zhao W, Stolz DB, Venkataramanan R, Lauffenburger D, Griffith L, Wells A. 2016. A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties. Lab Chip 17(1):156–168.
4. Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN. 2014. Lessons learned from the fate of AstraZeneca's drug pipeline: A five-dimensional framework. Nat Rev Drug Discov 13(6):419–431.
5. Denayer T, Stöhr T, Van Roy M. 2014. Animal models in translational medicine: Validation and prediction. New Horizons Transl Med 2(1):5–11.
6. Deng X, Luyendyk JP, Ganey PE, Roth RA. 2009. Inflammatory stress and idiosyncratic hepatotoxicity: Hints from animal models. Pharmacol Rev 61(3):262–282.
7. Ding L, Yang L, Wang Z, Huang W. 2015. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B 5(2):135–144.
8. Domansky K, Inman W, Serdy J, Dash A, Lim MH, Griffith LG. 2010. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10(1):51–58.
9. Dwinell MB, Lugering N, Eckmann L, Kagnoff MF. 2001. Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells. Gastroenterology 120(1):49–59.
10. Ebrahimkhani MR, Neiman JA, Raredon MS, Hughes DJ, Griffith LG. 2014. Bioreactor technologies to support liver function in vitro. Adv Drug Deliv Rev 69-70:132–157.
11. Edington CD, Cirit M, Chen WLK, Clark AM, Wells A, Trumper DL, Griffith LG. 2017. Integration of systems biology with organs-on-chips to humanize therapeutic development. In SPIE BiOS, pp. 1006113–1006113. International Society for Optics and Photonics.
12. Esch MB, Mahler GJ, Stokol T, Shuler ML. 2014. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip 14(16):3081–3092.
13. Esch MB, Prot JM, Wang YI, Miller P, Llamas-Vidales JR, Naughton BA, Applegate DR, Shuler ML. 2015. Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow. Lab Chip 15(10):2269–2277.
14. Esch MB, Ueno H, Applegate DR, Shuler ML. 2016. Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue. Lab Chip 16(14):2719–2729.
15. Feaver RE, Cole BK, Lawson MJ, Hoang SA, Marukian S, Blackman BR, Figler RA, Sanyal AJ, Wamhoff BR, Dash A. 2016. Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis. JCI Insight 1(20):e90954.
16. Frey O, Misun PM, Fluri DA, Hengstler JG, Hierlemann A. 2014. Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun 5:4250.
17. Gardiner KR, Halliday MI, Barclay GR, Milne L, Brown D, Stephens S, Maxwell RJ, Rowlands BJ. 1995. Significance of systemic endotoxaemia in inflammatory bowel disease. Gut 36(6):897–901.
18. Giese C, Marx U. 2014. Human immunity in vitro—Solving immunogenicity and more. Adv Drug Deliv Rev 69:103–122.
19. Groom JR, Luster AD. 2011. CXCR3 ligands: Redundant, collaborative and antagonistic functions. Immunol Cell Biol 89(2):207–215.
20. Guo S, Al-Sadi R, Said HM, Ma TY. 2013. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 182(2):375–387.
21. Gustafsson M, Nestor CE, Zhang H, Barabasi AL, Baranzini S, Brunak S, Chung KF, Federoff HJ, Gavin AC, Meehan RR, Picotti P, Pujana MA, Rajewsky N, Smith KG, Sterk PJ, Villoslada P, Benson M. 2014. Modules, networks and systems medicine for understanding disease and aiding diagnosis. Genome Med 6(10):82.
22. Helander HF, Fandriks L. 2014. Surface area of the digestive tract—Revisited. Scand J Gastroenterol 49(6):681–689.
23. Huang SM, Zhao H, Lee JI, Reynolds K, Zhang L, Temple R, Lesko LJ. 2010. Therapeutic protein-drug interactions and implications for drug development. Clin Pharmacol Ther 87(4):497–503.
24. Huebsch N, Loskill P, Deveshwar N, Spencer CI, Judge LM, Mandegar MA, Fox BC, Mohamed TMA, Ma Z, Mathur A, Sheehan AM, Truong A, Saxton M, Yoo J, Srivastava D, Desai TA, So P-L, Healy KE, Conklin BR. 2016. Miniaturized iPS-cell-derived cardiac muscles for physiologically relevant drug response analyses. Scientific Rep 6:24726.
25. Huh D, Torisawa YS, Hamilton GA, Kim HJ, Ingber DE. 2012. Microengineered physiological biomimicry: Organs-on-chips. Lab Chip 12(12):2156–2164.
26. Inman W, Domansky K, Serdy J, Owens B, Trumper D, Griffith LG. 2007. Design, modeling and fabrication of a constant flow pneumatic micropump. J Micromech Microeng 17(5):891.
27. Iori E, Vinci B, Murphy E, Marescotti MC, Avogaro A, Ahluwalia A. 2012. Glucose and fatty acid metabolism in a 3 tissue in-vitro model challenged with normo- and hyperglycaemia. PLoS ONE 7(4):e34704.
28. Jacob A, Zhou M, Wu R, Wang P. 2009. The role of hepatic cytochrome P-450 in sepsis. Int J Clin Exp Med 2(3):203–211.
29. Jeon JS, Bersini S, Gilardi M, Dubini G, Charest JL, Moretti M, Kamm RD. 2015. Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proc Natl Acad Sci U S A 112(1):214–219.
30. Kim TH, Lee SH, Lee SM. 2011. Role of Kupffer cells in pathogenesis of sepsis-induced drug metabolizing dysfunction. FEBS J 278(13):2307–2317.
31. Kitamura T, Pollard JW. 2015. Therapeutic potential of chemokine signal inhibition for metastatic breast cancer. Pharmacol Res 100:266–270.
32. Kubinyi H. 2003. Drug research: Myths, hype and reality. Nat Rev Drug Discov 2(8):665–668.
33. Leblond F, Seidah NG, Precourt LP, Delvin E, Dominguez M, Levy E. 2009. Regulation of the proprotein convertase subtilisin/kexin type 9 in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 296(4):G805–G815.
34. Lee H, Kim DS, Ha SK, Choi I, Lee JM, Sung JH. 2017. A pumpless multi-organ-on-a-chip (MOC) combined with a pharmacokinetic-pharmacodynamic (PK-PD) model. Biotechnol Bioeng 114(2):432–443.
35. Liaskou E, Wilson DV, Oo YH. 2012. Innate immune cells in liver inflammation. Mediators Inflamm 2012:949157.
36. Long TJ, Cosgrove PA, Dunn RT, Stolz DB, Hamadeh H, Afshari C, McBride H, Griffith LG. 2016. Modeling therapeutic antibody-small molecule drug-drug interactions using a three-dimensional perfusable human liver coculture platform. Drug Metab Dispos 44(12):1940–1948.
37. Loskill P, Marcus SG, Mathur A, Reese WM, Healy KE. 2015. µOrgano: A Lego®-like plug & play system for modular multi-organ-chips. PLoS ONE 10(10):e0139587.
38. Maass C, Stokes CL, Griffith LG, Cirit M. 2017. Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS). Integrative Biol 9(4):290–302.
39. Mahler GJ, Esch MB, Tako E, Southard TL, Archer SD, Glahn RP, Shuler ML. 2012. Oral exposure to polystyrene nanoparticles affects iron absorption. Nat Nanotechnol 7(4):264–271.
40. Marshall JC. 1993. Immunologic dyshomeostasis in multiple organ failure: The gut-Liver axis. In: Faist E, Meakins JL, Schildberg FW, editors. Host defense dysfunction in trauma, shock and sepsis: Mechanisms and therapeutic approaches. Berlin, Heidelberg: Springer Berlin Heidelberg. p 243–252.
41. Maschmeyer I, Hasenberg T, Jaenicke A, Lindner M, Lorenz AK, Zech J, Garbe LA, Sonntag F, Hayden P, Ayehunie S, Lauster R, Marx U, Materne EM. 2015a. Chip-based human liver-intestine and liver-skin co-cultures–A first step toward systemic repeated dose substance testing in vitro. Eur J Pharm Biopharm 95(Pt A):77–87.
42. Maschmeyer I, Lorenz AK, Schimek K, Hasenberg T, Ramme AP, Hubner J, Lindner M, Drewell C, Bauer S, Thomas A, Sambo NS, Sonntag F, Lauster R, Marx U. 2015b. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15(12):2688–2699.
43. Materne EM, Ramme AP, Terrasso AP, Serra M, Alves PM, Brito C, Sakharov DA, Tonevitsky AG, Lauster R, Marx U. 2015. A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing. J Biotechnol 205:36–46.
44. Mathur A, Loskill P, Shao K, Huebsch N, Hong S, Marcus SG, Marks N, Mandegar M, Conklin BR, Lee LP, Healy KE. 2015. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci Rep 5:8883.
45. Mestas J, Hughes CCW. 2004. Of mice and not men: Differences between mouse and human immunology. J Immunol 172(5):2731–2738.
46. Miller PG, Shuler ML. 2016. Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol Bioeng 113(10):2213–2227.
47. Moraes C, Labuz JM, Leung BM, Inoue M, Chun T-H, Takayama S. 2013. On being the right size: Scaling effects in designing a human-on-a-chip. Int Biol 5(9):1149–1161.
48. Morgan ET. 2001. Regulation of cytochrome p450 by inflammatory mediators: Why and how? Drug Metab Dispos 29(3):207–212.
49. Nguyen TV, Ukairo O, Khetani SR, McVay M, Kanchagar C, Seghezzi W, Ayanoglu G, Irrechukwu O, Evers R. 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(5):774–785.
50. Noah TK, Donahue B, Shroyer NF. 2011. Intestinal development and differentiation. Exp Cell Res 317(19):2702–2710.
51. Nollevaux G, Deville C, El Moualij B, Zorzi W, Deloyer P, Schneider YJ, Peulen O, Dandrifosse G. 2006. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21). BMC Cell Biol 7:20.
52. Oleaga C, Bernabini C, Smith AS, Srinivasan B, Jackson M, McLamb W, Platt V, Bridges R, Cai Y, Santhanam N, Berry B, Najjar S, Akanda N, Guo X, Martin C, Ekman G, Esch MB, Langer J, Ouedraogo G, Cotovio J, Breton L, Shuler ML, Hickman JJ. 2016. Multi-organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep 6:20030.
53. Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A, Upadhyaya A, Kurzawski P, Wack KE, Stolz DB, Kamm R, Griffith LG. 2002a. A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 78(3):257–269.
54. Powers MJ, Janigian DM, Wack KE, Baker CS, Beer Stolz D, Griffith LG. 2002b. Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. Tissue Eng 8(3):499–513.
55. Prothero JW. 1982. Organ scaling in mammals: The liver. Comp Biochem Physiol A Comp Physiol 71(4):567–577.
56. Rebelo SP, Dehne EM, Brito C, Horland R, Alves PM, Marx U. 2016. Validation of bioreactor and human-on-a-chip devices for chemical safety assessment. Adv Exp Med Biol 856:299–316.
57. Roth A, Singer T. 2014. The application of 3D cell models to support drug safety assessment: Opportunities & challenges. Advanced Drug Deliv Rev 69–70:179–189.
58. Sarkar CA, Lauffenburger DA. 2003. Cell-level pharmacokinetic model of granulocyte colony-stimulating factor: Implications for ligand lifetime and potency in vivo. Mol Pharmacol 63(1):147–158.
59. Sarkar U, Ravindra KC, Large E, Young CL, Rivera-Burgos D, Yu J, Cirit M, Hughes DJ, Wishnok JS, Lauffenburger DA, Griffith LG, Tannenbaum SR. 2017. Integrated assessment of diclofenac biotransformation, pharmacokinetics, and omics -based toxicity in a 3D human liver -immunocompetent co -culture system. Drug Metab Dispos 45(7):855–866.
60. Sarkar U, Rivera-Burgos D, Large EM, Hughes DJ, Ravindra KC, Dyer RL, Ebrahimkhani MR, Wishnok JS, Griffith LG, Tannenbaum SR. 2015. Metabolite profiling and pharmacokinetic evaluation of hydrocortisone in a perfused three-dimensional human liver bioreactor. Drug Metab Dispos 43(7):1091–1099.
61. Sin A, Chin KC, Jamil MF, Kostov Y, Rao G, Shuler ML. 2004. The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors. Biotechnol Prog 20(1):338–345.
62. Singh UP, Venkataraman C, Singh R, Lillard JW, Jr. 2007. CXCR3 axis: Role in inflammatory bowel disease and its therapeutic implication. Endocr Metab Immune Disord Drug Targets 7(2):111–123.
63. Sobrino A, Phan DT, Datta R, Wang X, Hachey SJ, Romero-Lopez M, Gratton E, Lee AP, George SC, Hughes CC. 2016. 3D microtumors in vitro supported by perfused vascular networks. Sci Rep 6:31589.
64. Stokes CL, Cirit M, Lauffenburger DA. 2015. Physiome-on-a-chip: The challenge of “scaling” in design, operation, and translation of microphysiological systems. CPT Pharmacometrics Syst Pharmacol 4(10):559–562.
65. Sung JH, Esch MB, Prot JM, Long CJ, Smith A, Hickman JJ, Shuler ML. 2013. Microfabricated mammalian organ systems and their integration into models of whole animals and humans. Lab Chip 13(7):1201–1212.
66. Sung JH, Kam C, Shuler ML. 2010. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10(4):446–455.
67. Sung JH, Shuler ML. 2009. A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip 9(10):1385–1394.
68. Toepke MW, Beebe DJ. 2006. PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip 6(12):1484–1486.
69. Tsamandouras N, Kostrzewski T, Stokes CL, Griffith LG, Hughes DJ, Cirit M. 2017. Quantitative assessment of population variability in hepatic drug metabolism using a perfused three-dimensional human liver microphysiological system. J Pharmacol Exp Therap 360(1):95–105.
70. Ucciferri N, Sbrana T, Ahluwalia A. 2014. Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism. Front Bioeng Biotechnol 2:74.
71. VanDussen KL, Marinshaw JM, Shaikh N, Miyoshi H, Moon C, Tarr PI, Ciorba MA, Stappenbeck TS. 2015. Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Gut 64(6):911–920.
72. Viravaidya K, Sin A, Shuler ML. 2004. Development of a microscale cell culture analog to probe naphthalene toxicity. Biotechnol Prog 20(1):316–323.
73. Vivares A, Salle-Lefort S, Arabeyre-Fabre C, Ngo R, Penarier G, Bremond M, Moliner P, Gallas JF, Fabre G, Klieber S. 2015. Morphological behaviour and metabolic capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device. Xenobiotica 45(1):29–44.
74. Wheeler SE, Clark AM, Taylor DP, Young CL, Pillai VC, Stolz DB, Venkataramanan R, Lauffenburger D, Griffith L, Wells A. 2014. Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system. Br J Cancer 111(12):2342–2350.
75. Wikswo JP. 2014. The relevance and potential roles of microphysiological systems in biology and medicine. Exp Biol Med (Maywood) 239(9):1061–1072.
76. Wikswo JP, Curtis EL, Eagleton ZE, Evans BC, Kole A, Hofmeister LH, Matloff WJ. 2013. Scaling and systems biology for integrating multiple organs-on-a-chip. Lab Chip 13(18):3496–3511.
77. Yeruva S, Ramadori G, Raddatz D. 2008. NF-kappaB-dependent synergistic regulation of CXCL10 gene expression by IL-1beta and IFN-gamma in human intestinal epithelial cell lines. Int J Colorectal Dis 23(3):305–317.
78. Zhu L, Xia H, Wang Z, Fong ELS, Fan J, Tong WH, Seah YPD, Zhang W, Li Q, Yu H. 2016. A vertical-flow bioreactor array compacts hepatocytes for enhanced polarity and functions. Lab on a Chip 16(20):3898–3908.