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Cited by 98Liver Disease Diagnosis and Treatment3D Printing in Biomedical ResearchLiver physiology and pathology

Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

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Yang, Jiandong, Hirai, Yoshikazu, Iida, Kei, Ito, Shinji, Trumm, Marika, Terada, Shiho, Sakai, Risako, Tsuchiya, Toshiyuki +2 more·2023·Communications Biology
DOI 10.1038/s42003-023-04710-8PMC PMC10036655
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Abstract

Non-alcoholic fatty liver disease (NAFLD) afflicts a significant percentage of the population; however, no effective treatments have yet been established because of the unsuitability of in vitro assays and animal experimental models. Here, we present an integrated-gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) by co-culturing human gut and liver cell lines interconnected via microfluidics in a closed circulation loop, for the initiation and progression of NAFLD by treatment with free fatty acids (FFAs) for 1 and 7 days, respectively. Co-cultured Caco-2 gut-mimicking cells and HepG2 hepatocyte-like cells demonstrate the protective effects from apoptosis against FFAs treatment, whereas mono-cultured cells exhibit induced apoptosis. Phenotype and gene expression analyses reveal that the FFAs-treated gut and liver cells accumulated intracellular lipid droplets and show an increase in gene expression associated with a cellular response to copper ions and endoplasmic reticulum stress. As an in vitro human GLA model, the iGLC platform may serve as an alternative to animal experiments for investigating the mechanisms of NAFLD.

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  • Yang et al.'s "gut-liver-on-a-chip" model is the most physiologically complex of the platforms described, reproducing the axis of interorgan interaction with closed-loop circulation, and prolonged exposure (7 days) brings the model closer to the chronic pathogenesis of MASLD.

    “Yang et al.’s model (“gut–liver-on-a-chip”) is the most physiologically complex of the platforms described, reproducing the axis of interorgan interaction with closed-loop circulation. Prolonged exposure (7 days) brings the model closer to the chronic pathogenesis of MASLD.”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [135]

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  1. [1]Chalasani N The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases Hepatology 2018 67 328 357 10.1002/hep.29367 28714183 · DOI · Paper page
  2. [2]Younossi ZM Non-alcoholic fatty liver disease—a global public health perspective J. Hepatol. 2019 70 531 544 10.1016/j.jhep.2018.10.033 30414863 · DOI · Paper page
  3. [3]Byrne CD Targher G NAFLD: A multisystem disease J. Hepatol. 2015 62 S47 S64 10.1016/j.jhep.2014.12.012 25920090 · DOI
  4. [4]Friedman SL Neuschwander-Tetri BA Rinella M Sanyal AJ Mechanisms of NAFLD development and therapeutic strategies Nat. Med. 2018 24 908 922 10.1038/s41591-018-0104-9 29967350 PMC6553468 · DOI · Paper page
  5. [5]Estes C Razavi H Loomba R Younossi Z Sanyal AJ Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease Hepatology 2018 67 123 133 10.1002/hep.29466 28802062 PMC5767767 · DOI
  6. [6]Buzzetti E Pinzani M Tsochatzis EA The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD) Metabolism 2016 65 1038 1048 10.1016/j.metabol.2015.12.012 26823198 · DOI · Paper page
  7. [7]Wiest R Albillos A Trauner M Bajaj JS Jalan R Targeting the gut-liver axis in liver disease J. Hepatol. 2017 67 1084 1103 10.1016/j.jhep.2017.05.007 28526488 · DOI
  8. [8]Sumida Y Yoneda M Current and future pharmacological therapies for NAFLD/NASH J. Gastroenterol 2018 53 362 376 10.1007/s00535-017-1415-1 29247356 PMC5847174 · DOI
  9. [9]Ohtani N Kawada N Role of the gut–liver axis in liver inflammation, fibrosis, and cancer: a special focus on the gut microbiota relationship Hepatol. Commun. 2019 3 456 470 10.1002/hep4.1331 30976737 PMC6442695 · DOI · Paper page
  10. [12]Clemente MG Mandato C Poeta M Vajro P Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions World J. Gastroenterol. 2016 22 8078 8093 10.3748/wjg.v22.i36.8078 27688650 PMC5037077 · DOI
  11. [13]Rotman Y Sanyal AJ Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease Gut 2017 66 180 190 10.1136/gutjnl-2016-312431 27646933 · DOI
  12. [14]Abdalkader R Kamei KI Multi-corneal barrier-on-a-chip to recapitulate eye blinking shear stress forces Lab Chip 2020 20 1410 1417 10.1039/C9LC01256G 32202263 · DOI
  13. [15]Sung JH Wang YI Kim JH Lee JM Shuler ML Application of chemical reaction engineering principles to “body-on-a-chip” systems AIChE J. 2018 64 4351 4360 10.1002/aic.16448 31402795 PMC6688854 · DOI
  14. [16]Abaci HE Shuler ML Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling Integr. Biol. 2015 7 383 391 10.1039/C4IB00292J PMC4407827 25739725 · DOI
  15. [17]Ronaldson-Bouchard K Vunjak-Novakovic G Organs-on-a-chip: a fast track for engineered human tissues in drug development Cell Stem Cell 2018 22 310 324 10.1016/j.stem.2018.02.011 29499151 PMC5837068 · DOI · Paper page
  16. [18]Schurdak M Applications of the microphysiology systems database for experimental ADME-Tox and disease models Lab Chip 2020 20 1472 1492 10.1039/C9LC01047E 32211684 PMC7497411 · DOI
  17. [19]Grego S Systems biology for organotypic cell cultures ALTEX 2017 34 301 310 10.14573/altex.1608221 27846345 PMC12127970 · DOI
  18. [20]Lee SY Sung JH Gut–liver on a chip toward an in vitro model of hepatic steatosis Biotechnol. Bioeng. 2018 115 2817 2827 10.1002/bit.26793 29981260 · DOI
  19. [21]Müller FA Sturla SJ Human in vitro models of nonalcoholic fatty liver disease Curr. Opin. Toxicol 2019 16 9 16 10.1016/j.cotox.2019.03.001 · DOI · Paper page
  20. [22]Chen WLK Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk Biotechnol. Bioeng. 2017 114 2648 2659 10.1002/bit.26370 28667746 PMC5614865 · DOI · Paper page
  21. [24]Costa J Ahluwalia A Advances and Current Challenges in Intestinal in vitro Model Engineering: A Digest Front. Bioeng. Biotechnol 2019 7 1 14 10.3389/fbioe.2019.00144 31275931 PMC6591368 · DOI
  22. [25]De Gregorio V Intestine-liver axis on-chip reveals the intestinal protective role on hepatic damage by emulating ethanol first-pass metabolism Front. Bioeng. Biotechnol. 2020 8 163 10.3389/fbioe.2020.00163 32258006 PMC7090126 · DOI
  23. [26]Jeon JW Lee SH Kim D Sung JH In vitro hepatic steatosis model based on gut–liver-on-a-chip Biotechnol. Prog. 2021 37 1 13 10.1002/btpr.3121 33393209 · DOI
  24. [28]Wen X Yoshimoto K Yamanaka M Terada S Kamei K In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems Organs-on-a-Chip 2021 3 100010 10.1016/j.ooc.2021.100010 · DOI
  25. [29]Kamei KI Integrated heart/cancer on a chip to reproduce the side effects of anti-cancer drugs: In vitro RSC Adv. 2017 7 36777 36786 10.1039/C7RA07716E · DOI · Paper page
  26. [30]Yu ZTF Integrated microfluidic devices for combinatorial cell-based assays Biomed. Microdevices 2009 11 547 555 10.1007/s10544-008-9260-x 19130244 PMC2893875 · DOI
  27. [31]Kamei KI An integrated microfluidic culture device for quantitative analysis of human embryonic stem cells Lab Chip 2009 9 555 563 10.1039/B809105F 19190791 · DOI
  28. [32]Huang B Wu H Kim S Zare RN Coating of poly(dimethylsiloxane) with n-dodecyl-β-D-maltoside to minimize nonspecific protein adsorption Lab Chip 2005 5 1005 1007 10.1039/b509251e 16175253 · DOI
  29. [33]Kamei KI Phenotypic and transcriptional modulation of human pluripotent stem cells induced by nano/microfabrication materials Adv. Healthc. Mater. 2013 2 287 291 10.1002/adhm.201200283 23184815 · DOI
  30. [34]Regehr KJ Biological implications of polydimethylsiloxane-based microfluidic cell culture Lab Chip 2009 9 2132 2139 10.1039/b903043c 19606288 PMC2792742 · DOI · Paper page
  31. [35]Wong I Ho CM Surface molecular property modifications for poly(dimethylsiloxane) (PDMS) based microfluidic devices Microfluid. Nanofluidics 2009 7 291 306 10.1007/s10404-009-0443-4 20357909 PMC2847407 · DOI
  32. [37]Kulthong K Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners RSC Adv. 2018 8 32440 32453 10.1039/C8RA05430D 35547722 PMC9086222 · DOI
  33. [38]Gómez-Lechón MJ A human hepatocellular in vitro model to investigate steatosis Chem. Biol. Interact. 2007 165 106 116 10.1016/j.cbi.2006.11.004 17188672 · DOI · Paper page
  34. [41]Ogawa Y Palmitate-induced lipotoxicity is crucial for the pathogenesis of nonalcoholic fatty liver disease in cooperation with gut-derived endotoxin Sci. Rep. 2018 8 11365 10.1038/s41598-018-29735-6 30054551 PMC6063851 · DOI
  35. [42]McQuin C CellProfiler 3.0: Next-generation image processing for biology PLoS Biol. 2018 16 e2005970 10.1371/journal.pbio.2005970 29969450 PMC6029841 · DOI
  36. [43]Carpenter AE CellProfiler: image analysis software for identifying and quantifying cell phenotypes Genome Biol. 2006 7 R100 10.1186/gb-2006-7-10-r100 17076895 PMC1794559 · DOI
  37. [44]Sirenko O Hesley J Rusyn I Cromwell EF High-content high-throughput assays for characterizing the viability and morphology of human iPSC-derived neuronal cultures Assay Drug Dev. Technol. 2014 12 536 547 10.1089/adt.2014.592 25506803 PMC4270163 · DOI
  38. [45]Gilbert DF A novel multiplex cell viability assay for high-throughput RNAi screening PLoS ONE 2011 6 e28338 10.1371/journal.pone.0028338 22162763 PMC3230607 · DOI
  39. [47]Caldez MJ Bjorklund M Kaldis P Cell cycle regulation in NAFLD: when imbalanced metabolism limits cell division Hepatol. Int. 2020 14 463 474 10.1007/s12072-020-10066-6 32578019 PMC7366567 · DOI
  40. [48]Kulthong K Microfluidic chip for culturing intestinal epithelial cell layers: characterization and comparison of drug transport between dynamic and static models Toxicol. Vitr 2020 65 104815 10.1016/j.tiv.2020.104815 32119998 · DOI
  41. [49]Villenave R Human gut-on-a-chip supports polarized infection of coxsackie B1 virus in vitro PLoS ONE 2017 12 1 17 10.1371/journal.pone.0169412 PMC5287454 28146569 · DOI
  42. [51]Delon LC A systematic investigation of the effect of the fluid shear stress on Caco-2 cells towards the optimization of epithelial organ-on-chip models Biomaterials 2019 225 119521 10.1016/j.biomaterials.2019.119521 31600674 · DOI · Paper page
  43. [53]Wang X Fluid shear stress promotes autophagy in hepatocellular carcinoma cells Int. J. Biol. Sci. 2018 14 1277 1290 10.7150/ijbs.27055 30123076 PMC6097484 · DOI
  44. [54]Camakaris J Voskoboinik I Mercer JF Molecular mechanisms of copper homeostasis Biochem. Biophys. Res. Commun. 1999 261 225 232 10.1006/bbrc.1999.1073 10425169 · DOI
  45. [55]Khan S Zafar A Naseem I Redox cycling of copper by coumarin-di(2-picolyl)amine hybrid molecule leads to ROS-mediated modulation of redox scavengers, DNA damage and cell death in diethylnitrosamine induced hepatocellular carcinoma Bioorg. Chem. 2020 99 103818 10.1016/j.bioorg.2020.103818 32276135 · DOI
  46. [56]Parsekar SU DNA binding, cleavage and cytotoxicity studies of three mononuclear Cu(II) chloro-complexes containing N–S donor Schiff base ligands J. Biol. Inorg. Chem. 2018 23 1331 1349 10.1007/s00775-018-1620-2 30302601 · DOI
  47. [57]Foo JB Copper complex derived from S-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell BioMetals 2018 31 505 515 10.1007/s10534-018-0096-4 29623473 · DOI
  48. [58]Gori M Palmitic acid affects intestinal epithelial barrier integrity and permeability in vitro Antioxidants 2020 9 417 10.3390/antiox9050417 32414055 PMC7278681 · DOI
  49. [59]Storniolo CE Cabral M Busquets MA Martín-Venegas R Moreno JJ Dual behavior of long-chain fatty acids and their cyclooxygenase/lipoxygenase metabolites on human intestinal Caco-2 cell growth Front. Pharmacol 2020 11 529976 10.3389/fphar.2020.529976 33013380 PMC7500452 · DOI
  50. [60]Embade N Valeron PF Aznar S Lopez-Collazo E Lacal JC Apoptosis induced by Rac GTPase correlates with induction of FasL and ceramides production Mol. Biol. Cell 2000 11 4347 4358 10.1091/mbc.11.12.4347 11102528 PMC15077 · DOI
  51. [61]Simon S Schubert R Inhibitory effect of phospholipids on P-glycoprotein: cellular studies in Caco-2, MDCKII mdr1 and MDCKII wildtype cells and P-gp ATPase activity measurements Biochim. Biophys. Acta—Mol. Cell Biol. Lipids 2012 1821 1211 1223 10.1016/j.bbalip.2012.06.001 22691950 · DOI
  52. [62]Berryman S Matthews K Lee JH Duffy SP Ma H Image-based phenotyping of disaggregated cells using deep learning Commun. Biol 2020 3 674 10.1038/s42003-020-01399-x 33188302 PMC7666170 · DOI
  53. [63]Ramos MJ Bandiera L Menolascina F Fallowfield JA In vitro models for non-alcoholic fatty liver disease: Emerging platforms and their applications iScience 2022 25 103549 10.1016/j.isci.2021.103549 34977507 PMC8689151 · DOI · Paper page
  54. [64]Grouls M Differential gene expression in iPSC-derived human intestinal epithelial cell layers following exposure to two concentrations of butyrate, propionate and acetate Sci. Rep. 2022 12 1 15 10.1038/s41598-022-17296-8 35977967 PMC9385623 · DOI
  55. [65]Green CJ Studying non-alcoholic fatty liver disease: the ins and outs of in vivo, ex vivo and in vitro human models Horm. Mol. Biol. Clin. Investig. 2020 41 20180038 30098284
  56. [67]Ganji SH Kashyap ML Kamanna VS Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: Impact on non-alcoholic fatty liver disease Metabolism 2015 64 982 990 10.1016/j.metabol.2015.05.002 26024755 · DOI
  57. [68]Thomson JA Embryonic stem cell lines derived from human blastocysts Science 1998 282 1145 1147 10.1126/science.282.5391.1145 9804556 · DOI
  58. [69]Takahashi K Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell 2007 131 861 872 10.1016/j.cell.2007.11.019 18035408 · DOI · Paper page
  59. [70]Yu J Induced pluripotent stem cell lines derived from human somatic cells Science 2007 318 1917 1920 10.1126/science.1151526 18029452 · DOI · Paper page
  60. [71]Lowry WE Generation of human induced pluripotent stem cells from dermal fibroblasts Proc. Natl. Acad. Sci. USA 2008 105 2883 2888 10.1073/pnas.0711983105 18287077 PMC2268554 · DOI · Paper page
  61. [72]Makarova KS Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants Nat. Rev. Microbiol 2020 18 67 83 10.1038/s41579-019-0299-x 31857715 PMC8905525 · DOI
  62. [73]Yang, J. et al. Multilayered microfluidic device for controllable flow perfusion of gut-liver on a chip. 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers). 176–179 (IEEE, 2021).
  63. [74]van Meer BJ Small molecule absorption by PDMS in the context of drug response bioassays Biochem. Biophys. Res. Commun. 2017 482 323 328 10.1016/j.bbrc.2016.11.062 27856254 PMC5240851 · DOI · Paper page
  64. [75]Berthier E Young EWK Beebe D Engineers are from PDMS-land, Biologists are from Polystyrenia Lab Chip 2012 12 1224 1237 10.1039/c2lc20982a 22318426 · DOI
  65. [76]Huh D Reconstituting organ-level lung functions on a chip Science 2010 328 1662 1668 10.1126/science.1188302 20576885 PMC8335790 · DOI · Paper page
  66. [77]Yoshimoto K Recapitulation of human embryonic heartbeat to promote differentiation of hepatic endoderm to hepatoblasts Front. Bioeng. Biotechnol. 2020 8 1064 10.3389/fbioe.2020.568092 PMC7506096 33015019 · DOI
  67. [79]Liao S He Y Chu Y Liao H Wang Y Solvent-resistant and fully recyclable perfluoropolyether-based elastomer for microfluidic chip fabrication J. Mater. Chem. A 2019 7 16249 16256 10.1039/C9TA03661J · DOI
  68. [80]Campbell SB Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems ACS Biomater. Sci. Eng. 2020 7 2880 2899 10.1021/acsbiomaterials.0c00640 34275293 · DOI
  69. [81]Albillos A de Gottardi A Rescigno M The gut-liver axis in liver disease: pathophysiological basis for therapy J. Hepatol. 2020 72 558 577 10.1016/j.jhep.2019.10.003 31622696 · DOI · Paper page
  70. [82]Ma X Experimental study of numerical optimization for 3-D microstructuring using DMD-based grayscale lithography J. Microelectromech. Syst. 2015 24 1856 1867 10.1109/JMEMS.2015.2447548 · DOI
  71. [83]Kato, Y., Hirai, Y., Kamei, K., Tsuchiya, T. & Tabata, O. Microfluidic device to interconnect multiple organs via fluidic circulation: towards body-on-a-chip. 18th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers). 1549–1552 (IEEE, 2015).
  72. [84]Langmead B Salzberg SL Fast gapped-read alignment with Bowtie 2 Nat. Methods 2012 9 357 359 10.1038/nmeth.1923 22388286 PMC3322381 · DOI · Paper page
  73. [85]Dobin A STAR: Ultrafast universal RNA-seq aligner Bioinformatics 2013 29 15 21 10.1093/bioinformatics/bts635 23104886 PMC3530905 · DOI · Paper page
  74. [86]Hunt SE Ensembl variation resources Database 2018 2018 1 12 10.1093/database/bay119 PMC6310513 30576484 · DOI
  75. [87]Li B Dewey CN RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome BMC Bioinformatics 2011 12 323 10.1186/1471-2105-12-323 21816040 PMC3163565 · DOI · Paper page
  76. [88]Love MI Huber W Anders S Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Genome Biol 2014 15 550 10.1186/s13059-014-0550-8 25516281 PMC4302049 · DOI · Paper page
  77. [89]Wang J Vasaikar S Shi Z Greer M Zhang B WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit Nucleic Acids Res. 2017 45 W130 W137 10.1093/nar/gkx356 28472511 PMC5570149 · DOI

Authors
Yang, J., Hirai, Y., Iida, K., Ito, S., Trumm, M., Terada, S., Sakai, R., Tsuchiya, T., Tabata, O., & Kamei, K.-I.
Affiliations
  • Kyoto University (JP)
  • Kindai University (JP)
  • Shenyang Pharmaceutical University (CN)
Corresponding author
  • Hirai, Yoshikazu
  • Kamei, Ken-ichiro
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2023-03-23
Volume
6
Issue
1
Pages
310-310
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-023-04710-8
PMC
PMC10036655
OpenAlex
W4360612586
Cited by
98
References
89
Citations by year
2026: 35 · 2025: 27 · 2024: 23 · 2023: 10 · 2022: 2 · 2021: 1
FWCI
18.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
Funders
  • MEXT | Japan Society for the Promotion of Science (19H02572, 18KK0306, 16K14660, 17H02083, 21H01728)
  • Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering
  • Japan Agency for Medical Research and Development (17937667)
  • Terumo Foundation for Life Sciences and Arts
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
non-alcoholic fatty liver disease, gut-liver axis, organ-on-a-chip, Caco-2 cells, HepG2 cells, free fatty acids, apoptosis, lipid droplets, endoplasmic reticulum stress, in vitro disease model
MeSH terms
Animals, Humans, Caco-2 Cells, Lipid Metabolism, Lab-On-A-Chip Devices, Non-alcoholic Fatty Liver Disease

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