Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

Scientific Reports

Volumn 8, Issue 1, 2018, Pages

  Edington, Collin D ^a   Chen, Wen Li Kelly ^a   Geishecker, Emily ^a   Kassis, Timothy ^a,b   Soenksen, Luis R ^a,b   Bhushan, Brij M ^a,b   Freake, Duncan ^c   Kirschner, Jared ^c   Maass, Christian ^a   Tsamandouras, Nikolaos ^a   Valdez, Jorge ^a   Cook, Christi D ^a   Parent, Tom ^c   Snyder, Stephen ^c   Yu, Jiajie ^a   Suter, Emily ^a   Shockley, Michael ^a   Velazquez, Jason ^a   Velazquez, Jeremy J ^a   Stockdale, Linda ^a   Papps, Julia P ^a   Lee, Iris ^a   Vann, Nicholas ^a   Gamboa, Mario ^a   Labarge, Matthew E ^a   Zhong, Zhe ^a   Wang, Xin ^a   Boyer, Laurie A ^b   Lauffenburger, Douglas A ^a,b   Carrier, Rebecca L ^d   Communal, Catherine ^a   Tannenbaum, Steven R ^a   Stokes, Cynthia L ^e   Hughes, David J ^f   Rohatgi, Gaurav ^c   Trumper, David L ^a,b   Cirit, Murat ^a   Griffith, Linda G ^a   more..

^a Massachusetts Institute of Technology Cambridge   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c Northeastern University ^*  (United States)

^d Northeastern University   (United States)

^e Stokes Consulting   (United States)

^f Centre for Innovation and Enterprise   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DICLOFENAC;

ANIMAL; BIOLOGICAL MODEL; COCULTURE; HUMAN; LAB ON A CHIP; LIVER; METABOLISM; MICROCHIP ANALYSIS; PHENOTYPE; PRECLINICAL STUDY; PROCEDURES; RAT;

ANIMALS; COCULTURE TECHNIQUES; DICLOFENAC; DRUG EVALUATION, PRECLINICAL; HUMANS; LAB-ON-A-CHIP DEVICES; LIVER; MICROCHIP ANALYTICAL PROCEDURES; MODELS, BIOLOGICAL; PHENOTYPE; RATS;

EID: 85044195316     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-018-22749-0     Document Type: Article

References (89)

1. Mak, I., Evaniew, N. & M, G. Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res 6, 114-118 (2014).
2. Waring, M. J. et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov 14, 475-486, https://doi.org/10.1038/nrd4609 (2015).
3. Causes of clinical failures vary widely by therapeutic class, phase of study (Tufts CSDD Impact Report, 2013).
4. Cook, D. et al. Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat Rev Drug Discov 13, 419-431, https://doi.org/10.1038/nrd4309 (2014).
5. Stokes, C. L., Cirit, M. & Lauffenburger, D. A. Physiome-on-a-Chip: The Challenge of "Scaling" in Design, Operation, and Translation of Microphysiological Systems. CPT: Pharmacometrics & Systems Pharmacology, n/a-n/a, https://doi.org/10.1002/psp4.12042 (2015).
6. Fabre, K. M., Livingston, C. & Tagle, D. A. Organs-on-chips (microphysiological systems): tools to expedite efficacy and toxicity testing in human tissue. Experimental Biology and Medicine 239, 1073-1077, https://doi.org/10.1177/1535370214538916 (2014).
7. Marx, U. et al. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX 33, 272-321, https://doi.org/10.14573/altex.1603161 (2016).
8. Wikswo, J. P. The relevance and potential roles of microphysiological systems in biology and medicine. Exp Biol Med (Maywood) 239, 1061-1072, https://doi.org/10.1177/1535370214542068 (2014).
9. Skardal, A., Shupe, T. & Atala, A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov Today 21, 1399-1411, https://doi.org/10.1016/j.drudis.2016.07.003 (2016).
10. Yum, K., Hong, S. G., Healy, K. E. & Lee, L. P. Physiologically relevant organs on chips. Biotechnology Journal 9, 16-27, https://doi.org/10.1002/biot.201300187 (2014).
11. Esch, M. B. et al. How multi-organ microdevices can help foster drug development. Adv Drug Deliv Rev 69-70, 158-169, https://doi.org/10.1016/j.addr.2013.12.003 (2014).
12. Beebe, D. J., Ingber, D. E. & den Toonder, J. Organs on Chips 2013. Lab Chip 13, 3447-3448, https://doi.org/10.1039/c3lc90080k (2013).
13. Alépée, N. et al. t4 Workshop Report: State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology. ALTEX 31, 441-477 (2014).
14. Esch, E. W., Bahinski, A. & Huh, D. Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov 14, 248-260, https://doi.org/10.1038/nrd4539 (2015).
15. Viravaidya, K., Sin, A. & Shuler, M. L. Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity. Biotechnol Progress 20, 316-323 (2004).
16. Sung, J. H., Kam, C. & Shuler, M. L. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab on a Chip 10, 446-455, https://doi.org/10.1039/B917763A (2010).
17. Proctor, W. R. et al. Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury. Arch Toxicol 91, 2849-2863, https://doi.org/10.1007/s00204-017-2002-1 (2017).
18. Weber, E. J. et al. Development of a microphysiological model of human kidney proximal tubule function. Kidney Int 90, 627-637, https://doi.org/10.1016/j.kint.2016.06.011 (2016).
19. Vivares, A. et al. Morphological behaviour and metabolic capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device. Xenobiotica 45, 29-44, https://doi.org/10.3109/00498254.2014.944612 (2015).
20. Long, T. et al. Modeling Therapeutic Antibody-Small Molecule Drug-Drug Interactions Using a Three Dimensional Perfusable Human Liver Coculture Platform. Drug Metab Dispos 44, 1940-1948 (2016).
21. Conant, G. et al. High-Content Assessment of Cardiac Function Using Heart-on-a-Chip Devices as Drug Screening Model. Stem Cell Rev 13, 335-346, https://doi.org/10.1007/s12015-017-9736-2 (2017).
22. Schwartz, M. P. et al. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity. Proc Natl Acad Sci U S A 112, 12516-12521, https://doi.org/10.1073/pnas.1516645112 (2015).
23. Lee, P. J., Hung, P. J. & Lee, L. P. In Biotechnol. Bioeng. Vol. 97 1340-1346 (2007).
24. Vernetti, L. et al. Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle. Sci Rep 7, 42296, https://doi.org/10.1038/srep42296 (2017).
25. Dehne, E., Hasenberg, T. & Marx, U. The ascendance of microphysiological systems to solve the drug testing dilemma. Future Science OA 3, FSO185 (2017).
26. Chen, M. B. et al. On-chip human microvasculature assay for visualization and quantification of tumor cell extravasation dynamics. Nat Protoc 12, 865-880, https://doi.org/10.1038/nprot.2017.018 (2017).
27. Sobrino, A. et al. 3D microtumors in vitro supported by perfused vascular networks. Sci Rep 6, 31589, https://doi.org/10.1038/srep31589 (2016).
28. Bang, S. et al. A Low Permeability Microfluidic Blood-Brain Barrier Platform with Direct Contact between Perfusable Vascular Network and Astrocytes. Sci Rep 7, 8083, https://doi.org/10.1038/s41598-017-07416-0 (2017).
29. Wagner, I. et al. 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, 3538-3547, https://doi.org/10.1039/c3lc50234a (2013).
30. Chen, W. L. K. et al. Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk. Biotechnol Bioeng 114, 2648-2659, https://doi.org/10.1002/bit.26370 (2017).
31. Maschmeyer, I. et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15, 2688-2699, https://doi.org/10.1039/c5lc00392j (2015).
32. Esch, M. B., Ueno, H., Applegate, D. R. & Shuler, M. L. Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue. Lab Chip 16, 2719-2729, https://doi.org/10.1039/c6lc00461j (2016).
33. Skardal, A. et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep 7, 8837, https://doi.org/10.1038/s41598-017-08879-x (2017).
34. Zhang, Y. S. et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci USA 114, E2293-E2302, https://doi.org/10.1073/pnas.1612906114 (2017).
35. Oleaga, C. et al. Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep 6, 20030, https://doi.org/10.1038/srep20030 (2016).
36. Tsamandouras, N. et al. Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies. AAPS J 19, 1499-1512, https://doi.org/10.1208/s12248-017-0122-4 (2017).
37. Wikswo, J. P. et al. Scaling and systems biology for integrating multiple organs-on-a-chip. Lab on a Chip 13, 3496-3511, https://doi.org/10.1039/C3LC50243K (2013).
38. Yu, J. et al. Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPSIntegration. CPT Pharmacometrics Syst. Pharmacol. 4, 585-594 (2015).
39. Abaci, H. E. & Shuler, M. L. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling. Integr Biol (Camb) 7, 383-391, https://doi.org/10.1039/c4ib00292j (2015).
40. Ucciferri, N., Sbrana, T. & Ahluwalia, A. Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism. Front Bioeng Biotechnol 2, 74, https://doi.org/10.3389/fbioe.2014.00074 (2014).
41. Maass, C., Stokes, C. L., Griffith, L. G. & Cirit, M. Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS). Integr Biol (Camb) 9, 290-302, https://doi.org/10.1039/c6ib00243a (2017).
42. Sorger, P. K. et al. In An NIH white paper by the QSP workshop group. 1-48 (NIH Bethesda).
43. Tsamandouras, N. et al. Quantitative assessment of population variability in hepatic drug metabolism using a perfused 3D human liver microphysiological system. J Pharmacol Exp Ther. 360, 95-105, https://doi.org/10.1124/jpet.116.237495 (2017).
44. Powers, M. J. et al. A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 78, 257-269 (2002).
45. Inman, W. et al. Design, modeling and fabrication of a constant flow pneumatic micropump. J. Micromech. Microeng. 17, 891-899 (2007).
46. Wheeler, S. E. et al. Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system. Br J Cancer 111, 2342-2350 (2014).
47. Mills, M. & Estes, M. K. Physiologically relevant human tissue models for infectious diseases. Drug Discov Today 21, 1540-1552, https://doi.org/10.1016/j.drudis.2016.06.020 (2016).
48. Wira, C. R. et al. Epithelial cell secretions from the human female reproductive tract inhibit sexually transmitted pathogens and Candida albicans but not Lactobacillus. Mucosal Immunol 4, 335-342, https://doi.org/10.1038/mi.2010.72 (2011).
49. Bicker, J., Alves, G., Fortuna, A. & Falcao, A. Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review. Eur J Pharm Biopharm 87, 409-432, https://doi.org/10.1016/j.ejpb.2014.03.012 (2014).
50. Powers, M. et al. Functional Behavior of Primary Rat Liver Cells in a Three-Dimensional Perfused Microarray Bioreactor. Tissue Eng Part A 8, 499-513 (2002).
51. Dash, A. et al. Liver tissue engineering in the evaluation of drug safety. Expert Opin Drug Metab Toxicol 5, 1159-1174 (2009).
52. Domansky, K. et al. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10, 51-58 (2010).
53. Materne, E. M. et al. The multi-organ chip-a microfluidic platform for long-term multi-tissue coculture. J Vis Exp, e52526, 10.3791/52526 (2015).
54. Merad, M. & Manz, M. Dendritic cell homeostasis. Blood 113, 3418-3427, 10.1182/blood- (2009).
55. Davies, N. & Anderson, K. Clinical Pharmacokinetics of Diclofenac. Clin. Pharmacokinet. 33, 184-213 (1997).
56. Miller, P. G. & Shuler, M. L. Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol Bioeng 113, 2213-2227, https://doi.org/10.1002/bit.25989 (2016).
57. Prot, J. M. et al. First pass intestinal and liver metabolism of paracetamol in a microfluidic platform coupled with a mathematical modeling as a means of evaluating ADME processes in humans. Biotechnol Bioeng 111, 2027-2040, https://doi.org/10.1002/bit.25232 (2014).
58. Lu, H. et al. Microfluidic shear devices for quantitative analysis of cell adhesion. Anal. Chem. 76, 5257-5264 (2004).
59. Loskill, P. et al. WAT-on-a-chip: a physiologically relevant microfluidic system incorporating white adipose tissue. Lab Chip 17, 1645-1654, https://doi.org/10.1039/c6lc01590e (2017).
60. Abaci, H. E., Shen, Y. I., Tan, S. & Gerecht, S. Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease. Sci Rep 4, 4951, https://doi.org/10.1038/srep04951 (2014).
61. Loskill, P., Marcus, S. G., Mathur, A., Reese, W. M. & Healy, K. E. mu Organo: A Lego (R)-Like Plug & Play System for Modular Multi-Organ-Chips. Plos One 10, ARTN e0139587, https://doi.org/10.1371/journal.pone.0139587 (2015).
62. Mathur, A. et al. Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications. Scientific Reports 5, 8883, https://doi.org/10.1038/srep08883 http://www.nature.com/articles/srep08883-supplementary-information (2015).
63. Huh, D. et al. A Human Disease Model of Drug Toxicity-Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice. Science Translational Medicine 4, 159ra147-159ra147, https://doi.org/10.1126/scitranslmed.3004249 (2012).
64. Regehr, K. J. et al. Biological implications of polydimethylsiloxane-based microfluidic cell culture. Lab on a Chip 9, 2132-2139, https://doi.org/10.1039/b903043c (2009).
65. Halldorsson, S., Lucumi, E., Gomez-Sjoberg, R. & Fleming, R. M. Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices. Biosens Bioelectron 63, 218-231, https://doi.org/10.1016/j.bios.2014.07.029 (2015).
66. van Midwoud, P. M., Janse, A., Merema, M. T., Groothuis, G. M. & Verpoorte, E. Comparison of biocompatibility and adsorption properties of different plastics for advanced microfluidic cell and tissue culture models. Anal Chem 84, 3938-3944, https://doi.org/10.1021/ac300771z (2012).
67. Rennert, K. et al. A microfluidically perfused three dimensional human liver model. Biomaterials 71, 119-131, https://doi.org/10.1016/j.biomaterials.2015.08.043 (2015).
68. Lim, S. H. & Pavesi, A. Creating Multiple Organotypic Models on a Single 3D Cell Culture Platform. BioTechniques 62, https://doi.org/10.2144/000114526 (2017).
69. Kaigala, G. V., Lovchik, R. D. & Delamarche, E. Microfluidics in the "open space" for performing localized chemistry on biological interfaces. Angew Chem Int Ed Engl 51, 11224-11240, https://doi.org/10.1002/anie.201201798 (2012).
70. Ng, S. F., Rouse, J., Sanderson, D. & Eccleston, G. A Comparative Study of Transmembrane Diffusion and Permeation of Ibuprofen across Synthetic Membranes Using Franz Diffusion Cells. Pharmaceutics 2, 209-223, https://doi.org/10.3390/pharmaceutics2020209 (2010).
71. Kostrzewski, T. et al. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease. World J Gastroenterol 23, 204-215, https://doi.org/10.3748/wjg.v23.i2.204 (2017).
72. Blanchard, N. et al. Prediction of hepatic clearance using cryopreserved human hepatocytes: a comparison of serum and serum-free incubations. J Pharm Pharmacol 58, 633-641, https://doi.org/10.1211/jpp.58.5.0008 (2006).
73. Shibata, Y., Takahashi, H., Chiba, M. & Ishii, Y. Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method. Drug Metab Dispos 30, 892-896 (2002).
74. 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, 25187, https://doi.org/10.1038/srep25187 (2016).
75. Dash, A. et al. Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro. Am J Physiol Cell Physiol 304, C1053-1063, https://doi.org/10.1152/ajpcell.00331.2012 (2013).
76. Helms, H. C. et al. In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab 36, 862-890, https://doi.org/10.1177/0271678X16630991 (2016).
77. Fulcher, M. L. & Randell, S. H. Human nasal and tracheo-bronchial respiratory epithelial cell culture. Methods Mol. Biol. 945, 109-121 (2013).
78. Nollevaux, G. et al. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21). BMC Cell Biol 7, 20, https://doi.org/10.1186/1471-2121-7-20 (2006).
79. Chen, J. C. et al. Coculturing human endometrial epithelial cells and stromal fibroblasts alters cell-specific gene expression and cytokine production. Fertil Steril 100, 1132-1143, https://doi.org/10.1016/j.fertnstert.2013.06.007 (2013).
80. Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662-1668 (2010).
81. Cook, C. D. et al. Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function. Integr Biol (Camb) 9, 271-289, https://doi.org/10.1039/c6ib00245e (2017).
82. Valdez, J. et al. On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial-stromal communication networks. Biomaterials 130, 90-103, https://doi.org/10.1016/j.biomaterials.2017.03.030 (2017).
83. Boretto, M. et al. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development 144, 1775-1786, https://doi.org/10.1242/dev.148478 (2017).
84. Turco, M. Y. et al. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nat Cell Biol 19, 568-577, https://doi.org/10.1038/ncb3516 (2017).
85. Sato, T. & Clevers, H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190-1194 (2013).
86. Sampson, T. R. et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell 167, 1469-1480 e1412, https://doi.org/10.1016/j.cell.2016.11.018 (2016).
87. Wikswo, J. et al. Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multiformulators and applications of the same. USA patent (2017).
88. Lacy, P. & Kostianovsky, M. Methods for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35-39 (1967).
89. Delanne, T., Lelièvre, D. & Cotovio, J. Towards a standardized trans-epithelial electrical resistance measurement on in vitro cutaneous and ocular reconstructed models. ALTEX Archiv-Suppl. Linz 08 (2008).