The ultimate goal of most biomedical research is to gain greater insight into mechanisms of human disease or to develop new and improved therapies or diagnostics. Although great advances have been made in terms of developing disease models in animals, such as transgenic mice, many of these models fail to faithfully recapitulate the human condition. In addition, it is difficult to identify critical cellular and molecular contributors to disease or to vary them independently in whole-animal models. This challenge has attracted the interest of engineers, who have begun to collaborate with biologists to leverage recent advances in tissue engineering and microfabrication to develop novel in vitro models of disease. As these models are synthetic systems, specific molecular factors and individual cell types, including parenchymal cells, vascular cells, and immune cells, can be varied independently while simultaneously measuring system-level responses in real time. In this article, we provide some examples of these efforts, including engineered models of diseases of the heart, lung, intestine, liver, kidney, cartilage, skin and vascular, endocrine, musculoskeletal, and nervous systems, as well as models of infectious diseases and cancer. We also describe how engineered in vitro models can be combined with human inducible pluripotent stem cells to enable new insights into a broad variety of disease mechanisms, as well as provide a test bed for screening new therapies.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV. 1.  et al. 2013. Genomic responses in mouse models poorly mimic human inflammatory diseases. PNAS 110:3507–12 [Google Scholar]
  2. Takahashi K, Yamanaka S. 2.  2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–76 [Google Scholar]
  3. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T. 3.  et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–72 [Google Scholar]
  4. Yu JY, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL. 4.  et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–20 [Google Scholar]
  5. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y. 5.  et al. 2010. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–86 [Google Scholar]
  6. Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR. 6.  et al. 2011. Induction of human neuronal cells by defined transcription factors. Nature 476:220–23 [Google Scholar]
  7. Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF. 7.  et al. 2011. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9:205–18 [Google Scholar]
  8. Singhvi R, Kumar A, Lopez G, Stephanopoulos GN, Wang DIC. 8.  et al. 1994. Engineering cell shape and function. Science 264:696–98 [Google Scholar]
  9. Chen CS, Mrksich M, Huang S, Whitesides G, Ingber DE. 9.  1997. Geometric control of cell life and death. Science 276:1425–28 [Google Scholar]
  10. Derda R, Musah S, Orner BP, Klim JR, Li L, Kiessling LL. 10.  2010. High-throughput discovery of synthetic surfaces that support proliferation of pluripotent cells. J. Am. Chem. Soc. 132:1289–95 [Google Scholar]
  11. Musah S, Morin SA, Wrighton PJ, Zwick DB, Jin S, Kiessling LL. 11.  2012. Glycosaminoglycan-binding hydrogels enable mechanical control of human pluripotent stem cell self-renewal. ACS Nano 6:10168–77 [Google Scholar]
  12. Shin SR, Jung SM, Zalabany M, Kim K, Zorlutuna P. 12.  et al. 2013. Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. ACS Nano 7:2369–80 [Google Scholar]
  13. Martin I, Wendt D, Heberer M. 13.  2004. The role of bioreactors in tissue engineering. Trends Biotechnol. 22:80–86 [Google Scholar]
  14. Huh D, Kim HJ, Fraser JP, Shea DE, Khan M. 14.  et al. 2013. Microfabrication of human organs-on-chips. Nat. Protoc. 8:2135–57 [Google Scholar]
  15. Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA. 15.  2014. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv. Mater. 26:3124–30 [Google Scholar]
  16. Yadid M, Sela G, Amiad Pavlov D, Landesberg A. 16.  2011. Adaptive control of cardiac contraction to changes in loading: from theory of sarcomere dynamics to whole-heart function. Pflügers Arch. 462:49–60 [Google Scholar]
  17. Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O. 17.  et al. 2011. Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471:225–29 [Google Scholar]
  18. Moretti A, Bellin M, Welling A, Jung CB, Lam JT. 18.  et al. 2010. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N. Engl. J. Med. 363:1397–409 [Google Scholar]
  19. Davis RP, Casini S, van den Berg CW, Hoekstra M, Remme CA. 19.  et al. 2012. Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease. Circulation 125:3079–91 [Google Scholar]
  20. Jung CB, Moretti A, Mederos y Schnitzler M, Iop L, Storch U. 20.  et al. 2012. Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia. EMBO Mol. Med. 4:180–91 [Google Scholar]
  21. Sun N, Yazawa M, Liu J, Han L, Sanchez-Freire V. 21.  et al. 2012. Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Sci. Transl. Med. 4:130ra47 [Google Scholar]
  22. Morita H, Seidman J, Seidman CE. 22.  2005. Genetic causes of human heart failure. J. Clin. Investig. 115:518–26 [Google Scholar]
  23. Hajjar RJ, Zsebo K, Deckelbaum L, Thompson C, Rudy J. 23.  et al. 2008. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J. Card. Fail. 14:355–67 [Google Scholar]
  24. Seidman JG, Seidman C. 24.  2001. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 104:557–67 [Google Scholar]
  25. Maron BJ. 25.  2002. Hypertrophic cardiomyopathy: a systematic review. JAMA 287:1308–20 [Google Scholar]
  26. Lan F, Lee AS, Liang P, Sanchez-Freire V, Nguyen PK. 26.  et al. 2013. Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. Cell Stem Cell 12:101–13 [Google Scholar]
  27. Burridge PW, Keller G, Gold JD, Wu JC. 27.  2012. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10:16–28 [Google Scholar]
  28. Thomas SP, Kucera JP, Bircher-Lehmann L, Rudy Y, Saffitz JE, Kleber AG. 28.  2003. Impulse propagation in synthetic strands of neonatal cardiac myocytes with genetically reduced levels of connexin43. Circ. Res. 92:1209–16 [Google Scholar]
  29. Beauchamp P, Choby C, Desplantez T, de Peyer K, Green K. 29.  et al. 2004. Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice. Circ. Res. 95:170–78 [Google Scholar]
  30. Beauchamp P, Desplantez T, McCain ML, Li W, Asimaki A. 30.  et al. 2012. Electrical coupling and propagation in engineered ventricular myocardium with heterogeneous expression of connexin43. Circ. Res. 110:1445–53 [Google Scholar]
  31. Alford PW, Feinberg AW, Sheehy SP, Parker KK. 31.  2010. Biohybrid thin films for measuring contractility in engineered cardiovascular muscle. Biomaterials 31:3613–21 [Google Scholar]
  32. Bursac N, Parker KK, Iravanian S, Tung L. 32.  2002. Cardiomyocyte cultures with controlled macroscopic anisotropy: a model for functional electrophysiological studies of cardiac muscle. Circ. Res. 91:E45–54 [Google Scholar]
  33. Grosberg A, Alford PW, McCain ML, Parker KK. 33.  2011. Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. Lab Chip 11:4165–73 [Google Scholar]
  34. McCain ML, Parker KK. 34.  2011. Mechanotransduction: the role of mechanical stress, myocyte shape, and cytoskeletal architecture on cardiac function. Pflügers Arch. 462:89–104 [Google Scholar]
  35. Pong T, Adams WJ, Bray MA, Feinberg AW, Sheehy SP. 35.  et al. 2011. Hierarchical architecture influences calcium dynamics in engineered cardiac muscle. Exp. Biol. Med. 236:366–73 [Google Scholar]
  36. Kim DH, Lipke EA, Kim P, Cheong R, Thompson S. 36.  et al. 2010. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. PNAS 107:565–70 [Google Scholar]
  37. Chung CY, Bien H, Sobie EA, Dasari V, McKinnon D. 37.  et al. 2011. Hypertrophic phenotype in cardiac cell assemblies solely by structural cues and ensuing self-organization. FASEB J. 25:851–62 [Google Scholar]
  38. Desplantez T, McCain ML, Beauchamp P, Rigoli G, Rothen-Rutishauser B. 38.  et al. 2012. Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current. Cardiovasc. Res. 94:58–65 [Google Scholar]
  39. Chang MG, Zhang YB, Chang CY, Xu LM, Emokpae R. 39.  et al. 2009. Spiral waves and reentry dynamics in an in vitro model of the healed infarct border zone. Circ. Res. 105:1062–71 [Google Scholar]
  40. Ursell PC, Gardner PI, Albala A, Fenoglio JJ, Wit AL. 40.  1985. Structural and electrophysiological changes in the epicardial border zone of canine myocardial infarcts during infarct healing. Circ. Res. 56:436–51 [Google Scholar]
  41. Saffitz JE. 41.  2000. Regulation of intercellular coupling in acute and chronic heart disease. Braz. J. Med. Biol. Res. 33:407–13 [Google Scholar]
  42. Brown RD, Ambler SK, Mitchell MD, Long CS. 42.  2005. The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Annu. Rev. Pharmacol. Toxicol. 45:657–87 [Google Scholar]
  43. Thompson SA, Copeland CR, Reich DH, Tung L. 43.  2011. Mechanical coupling between myofibroblasts and cardiomyocytes slows electric conduction in fibrotic cell monolayers. Circulation 123:2083–93 [Google Scholar]
  44. Dobaczewski M, Bujak M, Zymek P, Ren G, Entman ML, Frangogiannis NG. 44.  2006. Extracellular matrix remodeling in canine and mouse myocardial infarcts. Cell Tissue Res. 324:475–88 [Google Scholar]
  45. Souders CA, Bowers SL, Baudino TA. 45.  2009. Cardiac fibroblast: the renaissance cell. Circ. Res. 105:1164–76 [Google Scholar]
  46. Rohr S. 46.  2012. Arrhythmogenic implications of fibroblast-myocyte interactions. Circ. Arrhythm. Electrophysiol. 5:442–52 [Google Scholar]
  47. Thompson SA, Blazeski A, Copeland CR, Cohen DM, Chen CS. 47.  et al. 2014. Acute slowing of cardiac conduction in response to myofibroblast coupling to cardiomyocytes through N-cadherin. J. Mol. Cell. Cardiol. 68:29–37 [Google Scholar]
  48. Boulaksil M, Winckel SK, Engelen MA, Stein M, van Veen TA. 48.  et al. 2010. Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias. Eur. J. Heart Fail. 12:913–21 [Google Scholar]
  49. Kitamura H, Ohnishi Y, Yoshida A, Okajima K, Azumi H. 49.  et al. 2002. Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia. J. Cardiovasc. Electrophysiol. 13:865–70 [Google Scholar]
  50. Gutstein DE, Morley GE, Vaidya D, Liu F, Chen FL. 50.  et al. 2001. Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction. Circulation 104:1194–99 [Google Scholar]
  51. Feinberg AW, Feigel A, Shevkoplyas SS, Sheehy S, Whitesides GM, Parker KK. 51.  2007. Muscular thin films for building actuators and powering devices. Science 317:1366–70 [Google Scholar]
  52. McCain ML, Sheehy SP, Grosberg A, Goss JA, Parker KK. 52.  2013. Recapitulating maladaptive, multiscale remodeling of failing myocardium on a chip. PNAS 110:9770–75 [Google Scholar]
  53. Gomez AM, Valdivia HH, Cheng H, Lederer MR, Santana LF. 53.  et al. 1997. Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276:800–6 [Google Scholar]
  54. Piacentino V III, Weber CR, Chen X, Weisser-Thomas J, Margulies KB. 54.  et al. 2003. Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ. Res. 92:651–58 [Google Scholar]
  55. Eschenhagen T, Fink C, Remmers U, Scholz H, Wattchow J. 55.  et al. 1997. Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. FASEB J. 11:683–94 [Google Scholar]
  56. Zimmermann WH, Fink C, Kralisch D, Remmers U, Weil J, Eschenhagen T. 56.  2000. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnol. Bioeng. 68:106–14 [Google Scholar]
  57. Tobita K, Liu LJ, Janczewski AM, Tinney JP, Nonemaker JM. 57.  et al. 2006. Engineered early embryonic cardiac tissue retains proliferative and contractile properties of developing embryonic myocardium. Am. J. Physiol. Heart Circ. Physiol. 291:H1829–37 [Google Scholar]
  58. Ralphe JC, de Lange WJ. 58.  2013. 3D engineered cardiac tissue models of human heart disease: learning more from our mice. Trends Cardiovasc. Med. 23:27–32 [Google Scholar]
  59. Hansen A, Eder A, Bonstrup M, Flato M, Mewe M. 59.  et al. 2010. Development of a drug screening platform based on engineered heart tissue. Circ. Res. 107:35–44 [Google Scholar]
  60. Stohr A, Friedrich FW, Flenner F, Geertz B, Eder A. 60.  et al. 2013. Contractile abnormalities and altered drug response in engineered heart tissue from Mybpc3-targeted knock-in mice. J. Mol. Cell. Cardiol. 63:189–98 [Google Scholar]
  61. Vignier N, Schlossarek S, Fraysse B, Mearini G, Kramer E. 61.  et al. 2009. Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cardiac myosin-binding protein C mutant levels in cardiomyopathic mice. Circ. Res. 105:239–48 [Google Scholar]
  62. Fraysse B, Weinberger F, Bardswell SC, Cuello F, Vignier N. 62.  et al. 2012. Increased myofilament Ca2+ sensitivity and diastolic dysfunction as early consequences of Mybpc3 mutation in heterozygous knock-in mice. J. Mol. Cell. Cardiol. 52:1299–307 [Google Scholar]
  63. Pohlmann L, Kroger I, Vignier N, Schlossarek S, Kramer E. 63.  et al. 2007. Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes. Circ. Res. 101:928–38 [Google Scholar]
  64. de Lange WJ, Hegge LF, Grimes AC, Tong CW, Brost TM. 64.  et al. 2011. Neonatal mouse-derived engineered cardiac tissue: a novel model system for studying genetic heart disease. Circ. Res. 109:8–19 [Google Scholar]
  65. Radisic M, Park H, Gerecht S, Cannizzaro C, Langer R, Vunjak-Novakovic G. 65.  2007. Biomimetic approach to cardiac tissue engineering. Philos. Trans. R. Soc. B 362:1357–68 [Google Scholar]
  66. Song H, Zandstra PW, Radisic M. 66.  2011. Engineered heart tissue model of diabetic myocardium. Tissue Eng. A 17:1869–78 [Google Scholar]
  67. Katare RG, Ando M, Kakinuma Y, Sato T. 67.  2010. Engineered heart tissue: a novel tool to study the ischemic changes of the heart in vitro. PLOS ONE 5:e9275 [Google Scholar]
  68. Ando M, Katare RG, Kakinuma Y, Zhang D, Yamasaki F. 68.  et al. 2005. Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein. Circulation 112:164–70 [Google Scholar]
  69. Katare RG, Ando M, Kakinuma Y, Arikawa M, Handa T. 69.  et al. 2009. Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac effect. J. Thorac. Cardiovasc. Surg. 137:223–31 [Google Scholar]
  70. Kakinuma Y, Ando M, Kuwabara M, Katare RG, Okudela K. 70.  et al. 2005. Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1α. FEBS Lett. 579:2111–18 [Google Scholar]
  71. Mosadegh B, Dabiri BE, Lockett MR, Derda R, Campbell P. 71.  et al. 2014. Three-dimensional paper-based model for cardiac ischemia. Adv. Healthc. Mater. 3:1036–43 [Google Scholar]
  72. Deiss F, Mazzeo A, Hong E, Ingber DE, Derda R, Whitesides GM. 72.  2013. Platform for high-throughput testing of the effect of soluble compounds on 3D cell cultures. Anal. Chem. 85:8085–94 [Google Scholar]
  73. Derda R, Laromaine A, Mammoto A, Tang SK, Mammoto T. 73.  et al. 2009. Paper-supported 3D cell culture for tissue-based bioassays. PNAS 106:18457–62 [Google Scholar]
  74. Derda R, Tang SK, Laromaine A, Mosadegh B, Hong E. 74.  et al. 2011. Multizone paper platform for 3D cell cultures. PLOS ONE 6:e18940 [Google Scholar]
  75. Ma Z, Koo S, Finnegan MA, Loskill P, Huebsch N. 75.  et al. 2014. Three-dimensional filamentous human diseased cardiac tissue model. Biomaterials 35:1367–77 [Google Scholar]
  76. Koroleva A, Gill AA, Ortega I, Haycock JW, Schlie S. 76.  et al. 2012. Two-photon polymerization-generated and micromolding-replicated 3D scaffolds for peripheral neural tissue engineering applications. Biofabrication 4:025005 [Google Scholar]
  77. Hinton RB Jr, Lincoln J, Deutsch GH, Osinska H, Manning PB. 77.  et al. 2006. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ. Res. 98:1431–38 [Google Scholar]
  78. Butcher JT, Mahler GJ, Hockaday LA. 78.  2011. Aortic valve disease and treatment: the need for naturally engineered solutions. Adv. Drug Deliv. Rev. 63:242–68 [Google Scholar]
  79. Brinkley DM, Gelfand EV. 79.  2013. Valvular heart disease: classic teaching and emerging paradigms. Am. J. Med. 126:1035–42 [Google Scholar]
  80. Liu AC, Joag VR, Gotlieb AI. 80.  2007. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am. J. Pathol. 171:1407–18 [Google Scholar]
  81. Rajamannan NM, Evans FJ, Aikawa E, Grande-Allen KJ, Demer LL. 81.  et al. 2011. Calcific aortic valve disease: not simply a degenerative process. A review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: calcific aortic valve disease—2011 update. Circulation 124:1783–91 [Google Scholar]
  82. Yip CY, Simmons CA. 82.  2011. The aortic valve microenvironment and its role in calcific aortic valve disease. Cardiovasc. Pathol. 20:177–82 [Google Scholar]
  83. Wylie-Sears J, Aikawa E, Levine RA, Yang JH, Bischoff J. 83.  2011. Mitral valve endothelial cells with osteogenic differentiation potential. Arterioscler. Thromb. Vasc. Biol. 31:598–607 [Google Scholar]
  84. Gould ST, Srigunapalan S, Simmons CA, Anseth KS. 84.  2013. Hemodynamic and cellular response feedback in calcific aortic valve disease. Circ. Res. 113:186–97 [Google Scholar]
  85. van der Linde D, Konings EEM, Slager MA, Witsenburg M, Helbing WA. 85.  et al. 2011. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J. Am. Coll. Cardiol. 58:2241–47 [Google Scholar]
  86. Sider KL, Blaser MC, Simmons CA. 86.  2011. Animal models of calcific aortic valve disease. Int. J. Inflamm. 2011:364310 [Google Scholar]
  87. Arden C, Chambers JB, Sandoe J, Ray S, Prendergast B. 87.  et al. 2014. Can we improve the detection of heart valve disease. Heart 100:271–73 [Google Scholar]
  88. Yip CY, Chen JH, Zhao R, Simmons CA. 88.  2009. Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler. Thromb. Vasc. Biol. 29:936–42 [Google Scholar]
  89. Chen JH, Chen WL, Sider KL, Yip CY, Simmons CA. 89.  2011. β-Catenin mediates mechanically regulated, transforming growth factor-β1–induced myofibroblast differentiation of aortic valve interstitial cells. Arterioscler. Thromb Vasc. Biol. 31:590–97 [Google Scholar]
  90. Wang H, Haeger SM, Kloxin AM, Leinwand LA, Anseth KS. 90.  2012. Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus. PLOS ONE 7:e39969 [Google Scholar]
  91. Richards J, El-Hamamsy I, Chen S, Sarang Z, Sarathchandra P. 91.  et al. 2013. Side-specific endothelial-dependent regulation of aortic valve calcification: interplay of hemodynamics and nitric oxide signaling. Am. J. Pathol. 182:1922–31 [Google Scholar]
  92. Tseng H, Cuchiara ML, Durst CA, Cuchiara MP, Lin CJ. 92.  et al. 2013. Fabrication and mechanical evaluation of anatomically-inspired quasilaminate hydrogel structures with layer-specific formulations. Ann. Biomed. Eng. 41:398–407 [Google Scholar]
  93. Hockaday LA, Kang KH, Colangelo NW, Cheung PY, Duan B. 93.  et al. 2012. Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds. Biofabrication 4:035005 [Google Scholar]
  94. Duan B, Kapetanovic E, Hockaday LA, Butcher JT. 94.  2013. Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells. Acta Biomater. 10:1836–46 [Google Scholar]
  95. Young EW, Wheeler AR, Simmons CA. 95.  2007. Matrix-dependent adhesion of vascular and valvular endothelial cells in microfluidic channels. Lab Chip 7:1759–66 [Google Scholar]
  96. Chen MB, Srigunapalan S, Wheeler AR, Simmons CA. 96.  2013. A 3D microfluidic platform incorporating methacrylated gelatin hydrogels to study physiological cardiovascular cell-cell interactions. Lab Chip 13:2591–98 [Google Scholar]
  97. Thayer P, Balachandran K, Rathan S, Yap CH, Arjunon S. 97.  et al. 2011. The effects of combined cyclic stretch and pressure on the aortic valve interstitial cell phenotype. Ann. Biomed. Eng. 39:1654–67 [Google Scholar]
  98. Balachandran K, Alford PW, Wylie-Sears J, Goss JA, Grosberg A. 98.  et al. 2011. Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve. PNAS 108:19943–48 [Google Scholar]
  99. Moraes C, Likhitpanichkul M, Lam CJ, Beca BM, Sun Y, Simmons CA. 99.  2013. Microdevice array-based identification of distinct mechanobiological response profiles in layer-specific valve interstitial cells. Integr. Biol. 5:673–80 [Google Scholar]
  100. Wikswo JP, Curtis EL, Eagleton ZE, Evans BC, Kole A. 100.  et al. 2013. Scaling and systems biology for integrating multiple organs-on-a-chip. Lab Chip 13:3496–511 [Google Scholar]
  101. Moraes C, Labuz JM, Leung BM, Inoue M, Chun TH, Takayama S. 101.  2013. On being the right size: scaling effects in designing a human-on-a-chip. Integr. Biol. 5:1149–61 [Google Scholar]
  102. Holgate ST. 102.  2008. Pathogenesis of asthma. Clin. Exp. Allergy 38:872–97 [Google Scholar]
  103. Szelenyi I. 103.  2000. Animal models of bronchial asthma. Inflamm. Res. 49:639–54 [Google Scholar]
  104. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB. 104.  et al. 1999. Interleukin-4 receptor in moderate atopic asthma: a phase I/II randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 160:1816–23 [Google Scholar]
  105. Cho JY, Miller M, Baek KJ, Han JW, Nayar J. 105.  et al. 2004. Inhibition of airway remodeling in IL-5-deficient mice. J. Clin. Investig. 113:551–60 [Google Scholar]
  106. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. 106.  1996. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J. Exp. Med. 183:195–201 [Google Scholar]
  107. Hozawa S, Haruta Y, Ishioka S, Yamakido M. 107.  1995. Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma. Am. J. Respir. Crit. Care Med. 152:1198–202 [Google Scholar]
  108. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O'Connor BJ. 108.  et al. 2000. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356:2144–48 [Google Scholar]
  109. Norris V, Choong L, Tran D, Corden Z, Boyce M. 109.  et al. 2005. Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma. J. Allergy Clin. Immunol. 116:761–67 [Google Scholar]
  110. Hirst SJ. 110.  1996. Airway smooth muscle cell culture: application to studies of airway wall remodelling and phenotype plasticity in asthma. Eur. Respir. J. 9:808–20 [Google Scholar]
  111. Royce SG, Tan L, Koek AA, Tang ML. 111.  2009. Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma. Ann. Allergy Asthma Immunol. 102:238–46 [Google Scholar]
  112. Ingram JL, Huggins MJ, Church TD, Li Y, Francisco DC. 112.  et al. 2011. Airway fibroblasts in asthma manifest an invasive phenotype. Am. J. Respir. Crit. Care Med. 183:1625–32 [Google Scholar]
  113. Barbato A, Turato G, Baraldo S, Bazzan E, Calabrese F. 113.  et al. 2006. Epithelial damage and angiogenesis in the airways of children with asthma. Am. J. Respir. Crit. Care Med. 174:975–81 [Google Scholar]
  114. Yick CY, Ferreira DS, Annoni R, von der Thusen JH, Kunst PW. 114.  et al. 2012. Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma. Allergy 67:552–59 [Google Scholar]
  115. Parker J, Sarlang S, Thavagnanam S, Williamson G, O'Donoghue D. 115.  et al. 2010. A 3-D well-differentiated model of pediatric bronchial epithelium demonstrates unstimulated morphological differences between asthmatic and nonasthmatic cells. Pediatr. Res. 67:17–22 [Google Scholar]
  116. Blume C, Davies DE. 116.  2013. In vitro and ex vivo models of human asthma. Eur. J. Pharm. Biopharm. 84:394–400 [Google Scholar]
  117. Whitcutt MJ, Adler KB, Wu R. 117.  1988. A biphasic chamber system for maintaining polarity of differentiation of cultured respiratory tract epithelial cells. In Vitro Cell. Dev. Biol. 24:420–28 [Google Scholar]
  118. Gray TE, Guzman K, Davis CW, Abdullah LH, Nettesheim P. 118.  1996. Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 14:104–12 [Google Scholar]
  119. Thavagnanam S, Parker JC, McBrien ME, Skibinski G, Heaney LG. 119.  et al. 2011. Effects of IL-13 on mucociliary differentiation of pediatric asthmatic bronchial epithelial cells. Pediatr. Res. 69:95–100 [Google Scholar]
  120. Choe MM, Tomei AA, Swartz MA. 120.  2006. Physiological 3D tissue model of the airway wall and mucosa. Nat. Protoc. 1:357–62 [Google Scholar]
  121. Elias JA. 121.  2000. Airway remodeling in asthma: unanswered questions. Am. J. Respir. Crit. Care Med. 161:S168–71 [Google Scholar]
  122. Huang X, Yang N, Fiore VF, Barker TH, Sun Y. 122.  et al. 2012. Matrix stiffness–induced myofibroblast differentiation is mediated by intrinsic mechanotransduction. Am. J. Respir Cell Mol. Biol. 47:340–48 [Google Scholar]
  123. Miller C, George S, Niklason L. 123.  2010. Developing a tissue-engineered model of the human bronchiole. J. Tissue Eng. Regen. Med. 4:619–27 [Google Scholar]
  124. Krimmer DI, Oliver BG. 124.  2011. What can in vitro models of COPD tell us. Pulm. Pharmacol. Ther. 24:471–77 [Google Scholar]
  125. Adamson J, Haswell LE, Phillips G, Gaça MD. 125.  2011. In vitro models of chronic obstructive pulmonary disease (COPD). Bronchitis I Martin-Loeches 41–66 Rijeka, Croat.: InTech [Google Scholar]
  126. Rogers DF. 126.  2007. Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir. Care 52:1134–46 discussion 1146–49 [Google Scholar]
  127. Haswell LE, Hewitt K, Thorne D, Richter A, Gaça MD. 127.  2010. Cigarette smoke total particulate matter increases mucous secreting cell numbers in vitro: a potential model of goblet cell hyperplasia. Toxicol. In Vitro 24:981–87 [Google Scholar]
  128. Kreindler JL, Jackson AD, Kemp PA, Bridges RJ, Danahay H. 128.  2005. Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract. Am. J. Physiol. Lung Cell. Mol. Physiol. 288:L894–902 [Google Scholar]
  129. Comer DM, Kidney JC, Ennis M, Elborn JS. 129.  2013. Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers. Eur. Respir. J. 41:1058–67 [Google Scholar]
  130. Gray AC, McLeod JD, Clothier RH. 130.  2007. A review of in vitro modelling approaches to the identification and modulation of squamous metaplasia in the human tracheobronchial epithelium. Altern. Lab. Anim. 35:493–504 [Google Scholar]
  131. Korpi-Steiner NL, Valkenaar SM, Bates ME, Evans MD, Gern JE. 131.  et al. 2010. Human monocytic cells direct the robust release of CXCL10 by bronchial epithelial cells during rhinovirus infection. Clin. Exp. Allergy 40:1203–13 [Google Scholar]
  132. Araya J, Cambier S, Markovics JA, Wolters P, Jablons D. 132.  et al. 2007. Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients. J. Clin. Investig. 117:3551–62 [Google Scholar]
  133. Mukhopadhyay S, Gal AA. 133.  2010. Granulomatous lung disease: an approach to the differential diagnosis. Arch. Pathol. Lab. Med. 134:667–90 [Google Scholar]
  134. Heinemann DE, Peters JH, Gahr M. 134.  1997. A human in vitro granuloma model using heat killed Candida albicans cells immobilized on plastic culture wells. Scand. J. Immunol. 45:596–604 [Google Scholar]
  135. Puissegur MP, Botanch C, Duteyrat JL, Delsol G, Caratero C. 135.  et al. 2004. An in vitro dual model of mycobacterial granulomas to investigate the molecular interactions between mycobacteria and human host cells. Cell. Microbiol. 6:423–33 [Google Scholar]
  136. Shikama Y, Kobayashi K, Kasahara K, Kaga S, Hashimoto M. 136.  et al. 1989. Granuloma formation by artificial microparticles in vitro: Macrophages and monokines play a critical role in granuloma formation. Am. J. Pathol. 134:1189–99 [Google Scholar]
  137. Sanchez VC, Weston P, Yan A, Hurt RH, Kane AB. 137.  2011. A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials. Part. Fibre Toxicol. 8:17 [Google Scholar]
  138. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY. 138.  et al. 2010. Reconstituting organ-level lung functions on a chip. Science 328:1662–68 [Google Scholar]
  139. Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S. 139.  et al. 2012. A human disease model of drug toxicity–induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 4:159ra47 [Google Scholar]
  140. Rutgeerts P, Geboes K, Vantrappen G, Kerremans R, Coenegrachts JL. 140.  et al. 1984. Natural history of recurrent Crohn's disease at the ileocolonic anastomosis after curative surgery. Gut 25:665–72 [Google Scholar]
  141. Kaser A, Zeissig S, Blumberg RS. 141.  2010. Inflammatory bowel disease. Annu. Rev. Immunol. 28:573–621 [Google Scholar]
  142. Fang HW, Fang SB, Chiang Chiau JS, Yeung CY, Chan WT. 142.  et al. 2010. Inhibitory effects of Lactobacillus casei subsp. rhamnosus on Salmonella lipopolysaccharide-induced inflammation and epithelial barrier dysfunction in a co-culture model using Caco-2/peripheral blood mononuclear cells. J. Med. Microbiol. 59:573–79 [Google Scholar]
  143. Haller D, Bode C, Hammes WP, Pfeifer AM, Schiffrin EJ. 143.  et al. 2000. Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut 47:79–87 [Google Scholar]
  144. Parlesak A, Haller D, Brinz S, Baeuerlein A, Bode C. 144.  2004. Modulation of cytokine release by differentiated CACO-2 cells in a compartmentalized co-culture model with mononuclear leucocytes and nonpathogenic bacteria. Scand. J. Immunol. 60:477–85 [Google Scholar]
  145. Lievin-Le Moal V, Servin AL. 145.  2013. Pathogenesis of human enterovirulent bacteria: lessons from cultured, fully differentiated human colon cancer cell lines. Microbiol. Mol. Biol. Rev. 77:380–439 [Google Scholar]
  146. Mileti E, Matteoli G, Iliev ID, Rescigno M. 146.  2009. Comparison of the immunomodulatory properties of three probiotic strains of Lactobacilli using complex culture systems: prediction for in vivo efficacy. PLOS ONE 4:e7056 [Google Scholar]
  147. Nurmi JT, Puolakkainen PA, Rautonen NE. 147.  2005. Bifidobacterium lactis sp. 420 up-regulates cyclooxygenase (Cox)-1 and down-regulates Cox-2 gene expression in a Caco-2 cell culture model. Nutr. Cancer 51:83–92 [Google Scholar]
  148. Pozo-Rubio T, Mujico JR, Marcos A, Puertollano E, Nadal I. 148.  et al. 2011. Immunostimulatory effect of faecal Bifidobacterium species of breast-fed and formula-fed infants in a peripheral blood mononuclear cell/Caco-2 co-culture system. Br. J. Nutr. 106:1216–23 [Google Scholar]
  149. Sato T, Clevers H. 149.  2013. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340:1190–94 [Google Scholar]
  150. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE. 150.  et al. 2011. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470:105–9 [Google Scholar]
  151. McCracken KW, Howell JC, Wells JM, Spence JR. 151.  2011. Generating human intestinal tissue from pluripotent stem cells in vitro. Nat. Protoc. 6:1920–28 [Google Scholar]
  152. Kim HJ, Huh D, Hamilton G, Ingber DE. 152.  2012. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis–like motions and flow. Lab Chip 12:2165–74 [Google Scholar]
  153. Fiocchi C. 153.  1998. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115:182–205 [Google Scholar]
  154. Basson MD. 154.  2003. Paradigms for mechanical signal transduction in the intestinal epithelium. Digestion 68:217–25 [Google Scholar]
  155. Vantrappen G, Janssens J, Hellemans J, Ghoos Y. 155.  1977. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J. Clin. Investig. 59:1158–66 [Google Scholar]
  156. Quigley EM. 156.  2011. Microflora modulation of motility. J. Neurogastroenterol. Motil. 17:140–47 [Google Scholar]
  157. Kim HJ, Ingber DE. 157.  2013. Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr. Biol. 5:1130–40 [Google Scholar]
  158. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ. 158.  et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312:1355–59 [Google Scholar]
  159. Ley RE, Peterson DA, Gordon JI. 159.  2006. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124:837–48 [Google Scholar]
  160. Tremaroli V, Backhed F. 160.  2012. Functional interactions between the gut microbiota and host metabolism. Nature 489:242–49 [Google Scholar]
  161. Chantret I, Barbat A, Dussaulx E, Brattain MG, Zweibaum A. 161.  1988. Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. Cancer Res. 48:1936–42 [Google Scholar]
  162. De Palma G, Cinova J, Stepankova R, Tuckova L, Sanz Y. 162.  2010. Pivotal advance: Bifidobacteria and gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease. J. Leukoc. Biol. 87:765–78 [Google Scholar]
  163. Barrila J, Radtke AL, Crabbe A, Sarker SF, Herbst-Kralovetz MM. 163.  et al. 2010. Organotypic 3D cell culture models: using the rotating wall vessel to study host-pathogen interactions. Nat. Rev. Microbiol. 8:791–801 [Google Scholar]
  164. Höner zu Bentrup K, Ramamurthy R, Ott CM, Emami K, Nelman-Gonzalez M. 164.  et al. 2006. Three-dimensional organotypic models of human colonic epithelium to study the early stages of enteric salmonellosis. Microbes Infect. 8:1813–25 [Google Scholar]
  165. Margolis LB, Fitzgerald W, Glushakova S, Hatfill S, Amichay N. 165.  et al. 1997. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor. AIDS Res. Hum. Retrovir. 13:1411–20 [Google Scholar]
  166. Nickerson CA, Goodwin TJ, Terlonge J, Ott CM, Buchanan KL. 166.  et al. 2001. Three-dimensional tissue assemblies: novel models for the study of Salmonella enterica serovar Typhimurium pathogenesis. Infect. Immun. 69:7106–20 [Google Scholar]
  167. Nickerson CA, Richter EG, Ott CM. 167.  2007. Studying host-pathogen interactions in 3-D: organotypic models for infectious disease and drug development. J. Neuroimmune Pharmacol. 2:26–31 [Google Scholar]
  168. Sainz B Jr, TenCate V, Uprichard SL. 168.  2009. Three-dimensional Huh7 cell culture system for the study of hepatitis C virus infection. Virol. J. 6:103 [Google Scholar]
  169. Straub TM, Höner zu Bentrup K, Orosz-Coghlan P, Dohnalkova A, Mayer BK. 169.  et al. 2007. In vitro cell culture infectivity assay for human noroviruses. Emerg. Infect. Dis. 13:396–403 [Google Scholar]
  170. Papafragkou E, Hewitt J, Park GW, Greening G, Vinje J. 170.  2013. Challenges of culturing human norovirus in three-dimensional organoid intestinal cell culture models. PLOS ONE 8:e63485 [Google Scholar]
  171. Straub TM, Bartholomew RA, Valdez CO, Valentine NB, Dohnalkova A. 171.  et al. 2011. Human norovirus infection of Caco-2 cells grown as a three-dimensional tissue structure. J. Water Health 9:225–40 [Google Scholar]
  172. Finkbeiner SR, Zeng XL, Utama B, Atmar RL, Shroyer NF. 172.  et al. 2012. Stem cell–derived human intestinal organoids as an infection model for rotaviruses. mBio 3:e00159–12 [Google Scholar]
  173. Kalabis J, Wong GS, Vega ME, Natsuizaka M, Robertson ES. 173.  et al. 2012. Isolation and characterization of mouse and human esophageal epithelial cells in 3D organotypic culture. Nat. Protoc. 7:235–46 [Google Scholar]
  174. Klotz C, Aebischer T, Seeber F. 174.  2012. Stem cell–derived cell cultures and organoids for protozoan parasite propagation and studying host-parasite interaction. Int. J. Med. Microbiol. 302:203–9 [Google Scholar]
  175. Kuratnik A, Giardina C. 175.  2013. Intestinal organoids as tissue surrogates for toxicological and pharmacological studies. Biochem. Pharmacol. 85:1721–26 [Google Scholar]
  176. Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH. 176.  et al. 2011. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141:1762–72 [Google Scholar]
  177. Kim J, Hegde M, Jayaraman A. 177.  2010. Co-culture of epithelial cells and bacteria for investigating host-pathogen interactions. Lab Chip 10:43–50 [Google Scholar]
  178. Madl C, Druml W. 178.  2003. Systemic consequences of ileus. Best Pract. Res. Clin. Gastroenterol. 17:445–56 [Google Scholar]
  179. Lin HC. 179.  2004. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA 292:852–58 [Google Scholar]
  180. Bures J, Cyrany J, Kohoutova D, Forstl M, Rejchrt S. 180.  et al. 2010. Small intestinal bacterial overgrowth syndrome. World J. Gastroenterol. 16:2978–90 [Google Scholar]
  181. Schuller S, Lucas M, Kaper JB, Giron JA, Phillips AD. 181.  2009. The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coli infection. Cell. Microbiol. 11:521–30 [Google Scholar]
  182. Tsilingiri K, Barbosa T, Penna G, Caprioli F, Sonzogni A. 182.  et al. 2012. Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut 61:1007–15 [Google Scholar]
  183. Schuller S, Phillips AD. 183.  2010. Microaerobic conditions enhance type III secretion and adherence of enterohaemorrhagic Escherichia coli to polarized human intestinal epithelial cells. Environ. Microbiol. 12:2426–35 [Google Scholar]
  184. Duell BL, Cripps AW, Schembri MA, Ulett GC. 184.  2011. Epithelial cell co-culture models for studying infectious diseases: benefits and limitations. J. Biomed. Biotechnol. 2011:852419 [Google Scholar]
  185. Fritz JV, Desai MS, Shah P, Schneider JG, Wilmes P. 185.  2013. From meta-omics to causality: experimental models for human microbiome research. Microbiome 1:14 [Google Scholar]
  186. Soldatow VY, Lecluyse EL, Griffith LG, Rusyn I. 186.  2013. In vitro models for liver toxicity testing. Toxicol. Res. 2:23–39 [Google Scholar]
  187. Aizaki H, Nagamori S, Matsuda M, Kawakami H, Hashimoto O. 187.  et al. 2003. Production and release of infectious hepatitis C virus from human liver cell cultures in the three-dimensional radial-flow bioreactor. Virology 314:16–25 [Google Scholar]
  188. Sodunke TR, Bouchard MJ, Noh HM. 188.  2008. Microfluidic platform for hepatitis B viral replication study. Biomed. Microdevices 10:393–402 [Google Scholar]
  189. Schwartz RE, Trehan K, Andrus L, Sheahan TP, Ploss A. 189.  et al. 2012. Modeling hepatitis C virus infection using human induced pluripotent stem cells. PNAS 109:2544–48 [Google Scholar]
  190. Khetani SR, Bhatia SN. 190.  2008. Microscale culture of human liver cells for drug development. Nat. Biotechnol. 26:120–26 [Google Scholar]
  191. Ploss A, Khetani SR, Jones CT, Syder AJ, Trehan K. 191.  et al. 2010. Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures. PNAS 107:3141–45 [Google Scholar]
  192. March S, Ng S, Velmurugan S, Galstian A, Shan J. 192.  et al. 2013. A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax. Cell Host Microbe. 14:104–15 [Google Scholar]
  193. Gerbal-Chaloin S, Funakoshi N, Caillaud A, Gondeau C, Champon B, Si-Tayeb K. 193.  2014. Human induced pluripotent stem cells in hepatology: beyond the proof of concept. Am. J. Pathol. 184:332–47 [Google Scholar]
  194. Yanagida A, Ito K, Chikada H, Nakauchi H, Kamiya A. 194.  2013. An in vitro expansion system for generation of human IPS cell–derived hepatic progenitor–like cells exhibiting a bipotent differentiation potential. PLOS ONE 8:e67541 [Google Scholar]
  195. Nakamura N, Saeki K, Mitsumoto M, Matsuyama S, Nishio M. 195.  et al. 2012. Feeder-free and serum-free production of hepatocytes, cholangiocytes, and their proliferating progenitors from human pluripotent stem cells: application to liver-specific functional and cytotoxic assays. Cell. Reprogram. 14:171–85 [Google Scholar]
  196. Ordonez MP, Goldstein LSB. 196.  2012. Using human-induced pluripotent stem cells to model monogenic metabolic disorders of the liver. Semin. Liver Dis. 32:298–306 [Google Scholar]
  197. Fattahi F, Asgari S, Pournasr B, Seifinejad A, Totonchi M. 197.  et al. 2013. Disease-corrected hepatocyte-like cells from familial hypercholesterolemia–induced pluripotent stem cells. Mol. Biotechnol. 54:863–73 [Google Scholar]
  198. Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E. 198.  et al. 2010. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J. Clin. Investig. 120:3127–36 [Google Scholar]
  199. Ghodsizadeh A, Taei A, Totonchi M, Seifinejad A, Gourabi H. 199.  et al. 2010. Generation of liver disease–specific induced pluripotent stem cells along with efficient differentiation to functional hepatocyte-like cells. Stem Cell Rev. 6:622–32 [Google Scholar]
  200. Jang KJ, Mehr AP, Hamilton GA, McPartlin LA, Chung S. 200.  et al. 2013. Human kidney proximal tubule–on–a–chip for drug transport and nephrotoxicity assessment. Integr. Biol. 5:119–1129 [Google Scholar]
  201. Ludwig T, Riethmüller C, Gekle M, Schwerdt G, Oberleithner H. 201.  2004. Nephrotoxicity of platinum complexes is related to basolateral organic cation transport. Kidney Int. 66:196–202 [Google Scholar]
  202. Cornelison TL, Reed E. 202.  1993. Nephrotoxicity and hydration management for cisplatin, carboplatin, and ormaplatin. Gynecol. Oncol. 50:147–58 [Google Scholar]
  203. Yamada Y, Ikuta Y, Nosaka K, Miyanari N, Hayashi N. 203.  et al. 2010. Successful treatment of cisplatin overdose with plasma exchange. Case Rep. Med. 2010:802312 [Google Scholar]
  204. Yao X, Panichpisal K, Kurtzman N, Nugent K. 204.  2007. Cisplatin nephrotoxicity: a review. Am. J. Med. Sci. 334:115–24 [Google Scholar]
  205. Wallace DP, Grantham JJ, Sullivan LP. 205.  1996. Chloride and fluid secretion by cultured human polycystic kidney cells. Kidney Int. 50:1327–36 [Google Scholar]
  206. Yamaguchi T, Reif GA, Calvet JP, Wallace DP. 206.  2010. Sorafenib inhibits cAMP-dependent ERK activation, cell proliferation, and in vitro cyst growth of human ADPKD cyst epithelial cells. Am. J. Physiol. Ren. Physiol. 299:F944–51 [Google Scholar]
  207. DesRochers TM, Palma E, Kaplan DL. 207.  2014. Tissue-engineered kidney disease models. Adv. Drug Deliv. Rev. 69–70:67–80 [Google Scholar]
  208. Jansson K, Nguyen AT, Magenheimer BS, Reif GA, Aramadhaka LR. 208.  et al. 2012. Endogenous concentrations of ouabain act as a cofactor to stimulate fluid secretion and cyst growth of in vitro ADPKD models via cAMP and EGFR-Src-MEK pathways. Am. J. Physiol. Ren. Physiol. 303:F982–90 [Google Scholar]
  209. Aggarwal KP, Narula S, Kakkar M, Tandon C. 209.  2013. Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. Biomed. Res. Int. 2013:292953 [Google Scholar]
  210. Wei Z, Amponsah PK, Al-Shatti M, Nie Z, Bandyopadhyay BC. 210.  2012. Engineering of polarized tubular structures in a microfluidic device to study calcium phosphate stone formation. Lab Chip 12:4037–40 [Google Scholar]
  211. Moll S, Ebeling M, Weibel F, Farina A, Araujo Del Rosario A. 211.  et al. 2013. Epithelial cells as active player in fibrosis: findings from an in vitro model. PLOS ONE 8:e56575 [Google Scholar]
  212. Braccini A, Wendt JC, Jakob M, Heberer M, Jaquiery C. 212.  et al. 2005. Three-dimensional perfusion culture of human bone marrow cells and generation of osteoinductive grafts. Stem Cells 23:1066–72 [Google Scholar]
  213. Maggio ND, Piccinini E, Jaworski M, Trumpp A, Wendt DJ. 213.  et al. 2011. Toward modeling the bone marrow niche using scaffold-based 3D culture systems. Biomaterials 32:321–29 [Google Scholar]
  214. Nichols JE, Cortiella J, Lee J, Niles JA, Cuddihy M. 214.  et al. 2009. In vitro analog of human bone marrow from 3D scaffolds with biomimetic inverted colloidal crystal geometry. Biomaterials 30:1071–79 [Google Scholar]
  215. Sun H, Tsai Y, Nowak I, Dertinger SD, Wu JHD. 215.  et al. 2011. Response kinetics of radiation-induced micronucleated reticulocytes in human bone marrow culture. Mutat. Res. 718:38–43 [Google Scholar]
  216. Giese C, Demmler CD, Ammer R, Hartmann S, Lubitz A. 216.  et al. 2006. A human lymph node in vitro—challenges and progress. Artif. Organs 30:803–8 [Google Scholar]
  217. Giese C, Lubitz A, Demmler CD, Reuschel J, Bergner K. 217.  et al. 2010. Immunological substance testing on human lymphatic micro-organoids in vitro. J. Biotechnol. 148:38–45 [Google Scholar]
  218. Torisawa Y, Spina CS, Mammoto T, Mammoto A, Weaver JC. 218.  et al. 2014. Bone marrow–on–a–chip replicates hematopoietic niche physiology in vitro. Nat. Methods 11:663–69 [Google Scholar]
  219. Lee CY, Chan SH, Lai HY, Lee ST. 219.  2011. A method to develop an in vitro osteoporosis model of porcine vertebrae: histological and biomechanical study. J. Neurosurg. Spine 14:789–98 [Google Scholar]
  220. Chien S. 220.  2008. Effects of disturbed flow on endothelial cells. Ann. Biomed. Eng. 36:554–62 [Google Scholar]
  221. Li YS, Haga JH, Chien S. 221.  2005. Molecular basis of the effects of shear stress on vascular endothelial cells. J. Biomech. 38:1949–71 [Google Scholar]
  222. Sakariassen KS, Aarts PA, de Groot PG, Houdijk WP, Sixma JJ. 222.  1983. A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their extracellular matrix, and purified components. J. Lab. Clin. Med. 102:522–35 [Google Scholar]
  223. Van Kruchten R, Cosemans JM, Heemskerk JW. 223.  2012. Measurement of whole blood thrombus formation using parallel-plate flow chambers—a practical guide. Platelets 23:229–42 [Google Scholar]
  224. Penz S, Reininger AJ, Brandl R, Goyal P, Rabie T. 224.  et al. 2005. Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI. FASEB J. 19:898–909 [Google Scholar]
  225. Westein E, de Witt S, Lamers M, Cosemans JM, Heemskerk JW. 225.  2012. Monitoring in vitro thrombus formation with novel microfluidic devices. Platelets 23:501–9 [Google Scholar]
  226. Nesbitt WS, Westein E, Tovar-Lopez FJ, Tolouei E, Mitchell A. 226.  et al. 2009. A shear gradient–dependent platelet aggregation mechanism drives thrombus formation. Nat. Med. 15:665–73 [Google Scholar]
  227. Westein E, van der Meer AD, Kuijpers MJ, Frimat JP, van den Berg A, Heemskerk JW. 227.  2013. Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor–dependent manner. PNAS 110:1357–62 [Google Scholar]
  228. Karino T, Motomiya M. 228.  1984. Flow through a venous valve and its implication for thrombus formation. Thromb. Res. 36:245–57 [Google Scholar]
  229. Runyon MK, Kastrup CJ, Johnson-Kerner BL, Ha TG, Ismagilov RF. 229.  2008. Effects of shear rate on propagation of blood clotting determined using microfluidics and numerical simulations. J. Am. Chem. Soc. 130:3458–64 [Google Scholar]
  230. Takasu N, Ohno S, Komiya I, Yamada T. 230.  1992. Requirements of follicle structure for thyroid hormone synthesis; cytoskeletons and iodine metabolism in polarized monolayer cells on collagen gel and in double layered, follicle-forming cells. Endocrinology 131:1143–48 [Google Scholar]
  231. Toda S, Koike N, Sugihara H. 231.  2001. Cellular integration of thyrocytes and thyroid folliculogenesis: a perspective for thyroid tissue regeneration and engineering. Endocr. J. 48:407–25 [Google Scholar]
  232. Toda S, Koike N, Sugihara H. 232.  2001. Thyrocyte integration, and thyroid folliculogenesis and tissue regeneration: perspective for thyroid tissue engineering. Pathol. Int. 51:403–17 [Google Scholar]
  233. Toni R, Casa CD, Spaletta G, Marchetti G, Mazzoni P. 233.  et al. 2007. The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement. Acta Biomed. 78:Suppl. 1129–55 [Google Scholar]
  234. Toni R, Tampieri A, Zini N, Strusi V, Sandri M. 234.  et al. 2011. Ex situ bioengineering of bioartificial endocrine glands: a new frontier in regenerative medicine of soft tissue organs. Ann. Anat. 193:381–94 [Google Scholar]
  235. Xu M, West E, Shea LD, Woodruff TK. 235.  2006. Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development. Biol. Reprod. 75:916–23 [Google Scholar]
  236. Hovatta O, Silye R, Abir R, Krausz T, Winston RM. 236.  1997. Extracellular matrix improves survival of both stored and fresh human primordial and primary ovarian follicles in long-term culture. Hum. Reprod. 12:1032–36 [Google Scholar]
  237. Augst AD, Kong HJ, Mooney DJ. 237.  2006. Alginate hydrogels as biomaterials. Macromol. Biosci. 6:623–33 [Google Scholar]
  238. Kreeger PK, Deck JW, Woodruff TK, Shea LD. 238.  2006. The in vitro regulation of ovarian follicle development using alginate–extracellular matrix gels. Biomaterials 27:714–23 [Google Scholar]
  239. Pangas SA, Saudye H, Shea LD, Woodruff TK. 239.  2003. Novel approach for the three-dimensional culture of granulosa cell–oocyte complexes. Tissue Eng. 9:1013–21 [Google Scholar]
  240. Hornick JE, Duncan FE, Shea LD, Woodruff TK. 240.  2013. Multiple follicle culture supports primary follicle growth through paracrine-acting signals. Reproduction 145:19–32 [Google Scholar]
  241. Telfer EE, McLaughlin M, Ding C, Thong KJ. 241.  2008. A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Hum. Reprod. 23:1151–58 [Google Scholar]
  242. Tagler D, Makanji Y, Tu T, Bernabe BP, Lee R. 242.  et al. 2013. Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels. Biotechnol. Bioeng. 1111417–29
  243. Ting AY, Yeoman RR, Lawson MS, Zelinski MB. 243.  2012. Synthetic polymers improve vitrification outcomes of macaque ovarian tissue as assessed by histological integrity and the in vitro development of secondary follicles. Cryobiology 65:1–11 [Google Scholar]
  244. Telfer EE, Zelinski MB. 244.  2013. Ovarian follicle culture: advances and challenges for human and nonhuman primates. Fertil. Steril. 99:1523–33 [Google Scholar]
  245. Krotz SP, Robins JC, Ferruccio TM, Moore R, Steinhoff MM. 245.  et al. 2013. In vitro maturation of oocytes via the pre-fabricated self-assembled artificial human ovary. J. Assist. Reprod. Genet. 27:743–50 [Google Scholar]
  246. Coronel MM, Stabler CL. 246.  2013. Engineering a local microenvironment for pancreatic islet replacement. Curr. Opin. Biotechnol. 24:900–8 [Google Scholar]
  247. Phelps EA, Headen DM, Taylor WR, Thule PM, Garcia AJ. 247.  2013. Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes. Biomaterials 34:4602–11 [Google Scholar]
  248. Zhang Y, Jalili RB, Warnock GL, Ao Z, Marzban L, Ghahary A. 248.  2012. Three-dimensional scaffolds reduce islet amyloid formation and enhance survival and function of cultured human islets. Am. J. Pathol. 181:1296–305 [Google Scholar]
  249. Kaufman-Francis K, Koffler J, Weinberg N, Dor Y, Levenberg S. 249.  2012. Engineered vascular beds provide key signals to pancreatic hormone–producing cells. PLOS ONE 7:e40741 [Google Scholar]
  250. Kerr-Conte J, Pattou F, Lecomte-Houcke M, Xia Y, Boilly B. 250.  et al. 1996. Ductal cyst formation in collagen-embedded adult human islet preparations: a means to the reproduction of nesidioblastosis in vitro. Diabetes 45:1108–14 [Google Scholar]
  251. Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG. 251.  et al. 2008. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat. Biotechnol. 26:443–52 [Google Scholar]
  252. Jiang J, Au M, Lu K, Eshpeter A, Korbutt G. 252.  et al. 2007. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25:1940–53 [Google Scholar]
  253. Thatava T, Armstrong AS, De Lamo JG, Edukulla R, Khan YK. 253.  et al. 2011. Successful disease-specific induced pluripotent stem cell generation from patients with kidney transplantation. Stem Cell Res. Ther. 2:48 [Google Scholar]
  254. Cheng X, Ying L, Lu L, Galvao AM, Mills JA. 254.  et al. 2012. Self-renewing endodermal progenitor lines generated from human pluripotent stem cells. Cell Stem Cell 10:371–84 [Google Scholar]
  255. Prabakar KR, Domínguez-Bendala J, Molano RD, Pileggi A, Villate S. 255.  et al. 2012. Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood–derived mesenchymal stem cells. Cell Transplant. 21:1321–39 [Google Scholar]
  256. Woodford C, Zandstra PW. 256.  2012. Tissue engineering 2.0: guiding self-organization during pluripotent stem cell differentiation. Curr. Opin. Biotechnol. 23:810–19 [Google Scholar]
  257. Jun Y, Kang AR, Lee JS, Park SJ, Lee DY. 257.  et al. 2014. Microchip-based engineering of super-pancreatic islets supported by adipose-derived stem cells. Biomaterials 35:4815–26 [Google Scholar]
  258. Spiegelman BM. 258.  2013. Banting Lecture 2012. Regulation of adipogenesis: toward new therapeutics for metabolic disease. Diabetes 62:1774–82 [Google Scholar]
  259. Hotamisligil GS. 259.  2006. Inflammation and metabolic disorders. Nature 444:860–67 [Google Scholar]
  260. Gilbert CA, Slingerland JM. 260.  2013. Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression. Annu. Rev. Med. 64:45–57 [Google Scholar]
  261. Johnson AM, Olefsky JM. 261.  2012. The origins and drivers of insulin resistance. Cell 152:673–84 [Google Scholar]
  262. Fischbach C, Seufert J, Staiger H, Hacker M, Neubauer M. 262.  et al. 2004. Three-dimensional in vitro model of adipogenesis: comparison of culture conditions. Tissue Eng. 10:215–29 [Google Scholar]
  263. Kang X, Xie Y, Powell HM, Lee LJ, Belury MA. 263.  et al. 2007. Adipogenesis of murine embryonic stem cells in a three-dimensional culture system using electrospun polymer scaffolds. Biomaterials 28:450–58 [Google Scholar]
  264. Kang X, Xie Y, Kniss DA. 264.  2005. Adipose tissue model using three-dimensional cultivation of preadipocytes seeded onto fibrous polymer scaffolds. Tissue Eng. 11:458–68 [Google Scholar]
  265. Aoki S, Toda S, Sakemi T, Sugihara H. 265.  2003. Co-culture of endothelial cells and mature adipocytes actively promotes immature preadipocyte development in vitro. Cell Struct. Funct. 28:55–60 [Google Scholar]
  266. Choi JH, Bellas E, Vunjak-Novakovic G, Kaplan DL. 266.  2011. Adipogenic differentiation of human adipose-derived stem cells on 3D silk scaffolds. Methods Mol. Biol. 702:319–30 [Google Scholar]
  267. Daquinag AC, Souza GR, Kolonin MG. 267.  2013. Adipose tissue engineering in three-dimensional levitation tissue culture system based on magnetic nanoparticles. Tissue Eng. C 19:336–44 [Google Scholar]
  268. Choi JH, Gimble JM, Lee K, Marra KG, Rubin JP. 268.  et al. 2010. Adipose tissue engineering for soft tissue regeneration. Tissue Eng. B 16:413–26 [Google Scholar]
  269. Lai N, Sims JK, Jeon NL, Lee K. 269.  2012. Adipocyte induction of preadipocyte differentiation in a gradient chamber. Tissue Eng. C 18:958–67 [Google Scholar]
  270. Dennis RG, Kosnik PF. 270.  2000. Excitability and isometric contractile properties of mammalian skeletal muscle constructs engineered in vitro. In Vitro Cell. Dev. Biol. Anim. 36:327–35 [Google Scholar]
  271. Hosseini V, Ahadian S, Ostrovidov S, Camci-Unal G, Chen S. 271.  et al. 2012. Engineered contractile skeletal muscle tissue on a microgrooved methacrylated gelatin substrate. Tissue Eng. A 18:2453–65 [Google Scholar]
  272. Khodabukus A, Baar K. 272.  2012. Defined electrical stimulation emphasizing excitability for the development and testing of engineered skeletal muscle. Tissue Eng. C 18:349–57 [Google Scholar]
  273. Nagamine K, Kawashima T, Ishibashi T, Kaji H, Kanzaki M, Nishizawa M. 273.  2010. Micropatterning contractile C2C12 myotubes embedded in a fibrin gel. Biotechnol. Bioeng. 105:1161–67 [Google Scholar]
  274. Ramón-Azcón J, Ahadian S, Estili M, Liang X, Ostrovidov S. 274.  et al. 2013. Dielectrophoretically aligned carbon nanotubes to control electrical and mechanical properties of hydrogels to fabricate contractile muscle myofibers. Adv. Mater. 25:4028–34 [Google Scholar]
  275. Sakar MS, Neal D, Boudou T, Borochin MA, Li Y. 275.  et al. 2012. Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. Lab Chip 12:4976–85 [Google Scholar]
  276. Shimizu FHK, Nagamori E. 276.  2010. Novel method for measuring active tension generation by C2C12 myotube using UV-crosslinked collagen film. Biotechnol. Bioeng. 106:482–89 [Google Scholar]
  277. Shimizu FHK, Sasaki H, Hida H, Fujita H, Obinata K. 277.  et al. 2010. Assembly of skeletal muscle cells on a Si-MEMS device and their generative force measurement. Biomed. Microdevices 12:247–52 [Google Scholar]
  278. Vandenburgh H, Shansky J, Benesch-Lee F, Barbata V, Reid J. 278.  et al. 2008. A drug screening platform based on the contractility of tissue engineered muscle. Muscle Nerve 37:438–47 [Google Scholar]
  279. Wilson K, Das M, Wahl KJ, Colton RJ, Hickman JJ. 279.  2010. Measurement of contractile stress generated by cultured rat muscle on silicon cantilevers for toxin detection and muscle performance enhancement. PLOS ONE 5:e11042 [Google Scholar]
  280. Kaji H, Ishibashi T, Nagamine K, Kanzaki M, Nishizawa M. 280.  2010. Electrically induced contraction of C2C12 myotubes cultured on a porous membrane-based substrate with muscle tissue–like stiffness. Biomaterials 31:6981–86 [Google Scholar]
  281. Smith AST, Long CJ, Pirozzi K, Hickman JJ. 281.  2013. A functional system for high-content screening of neuromuscular junctions in vitro. Technology 1:1–12 [Google Scholar]
  282. Morimoto Y, Kato-Negishi M, Onoe H, Takeuchi S. 282.  2013. Three-dimensional neuron-muscle constructs with neuromuscular junctions. Biomaterials 34:9413–19 [Google Scholar]
  283. Sun Y, Duffy R, Lee A, Feinberg AW. 283.  2013. Optimizing the structure and contractility of engineered skeletal muscle thin films. Acta Biomater. 9:7885–94 [Google Scholar]
  284. Krook A, Björnholm M, Galuska D, Jiang XJ, Fahlman R. 284.  et al. 2000. Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes 49:284–92 [Google Scholar]
  285. Ishibashi T, Hoshino Y, Kaji H, Kanzaki M, Sato M, Nishizawa M. 285.  2009. Localized electrical stimulation to C2C12 myotubes cultured on a porous membrane-based substrate. Biomed. Microdevices 11:413–19 [Google Scholar]
  286. Nagamine K, Kawashima T, Sekine S, Ido Y, Kanzaki M, Nishizawa M. 286.  2010. Spatiotemporally controlled contraction of micropatterned skeletal muscle cells on a hydrogel sheet. Lab Chip 11:513–17 [Google Scholar]
  287. Sharples AP, Player DJ, Martin NR, Mudera V, Stewart CE, Lewis MP. 287.  2012. Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs. Aging Cell 11:986–95 [Google Scholar]
  288. Sharples AP, Al-Shanti N, Lewis MP, Stewart CE. 288.  2011. Reduction of myoblast differentiation following multiple population doublings in mouse C2C12 cells: a model to investigate ageing?. J. Cell. Biochem. 112:3773–85 [Google Scholar]
  289. Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T. 289.  et al. 2005. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 19:422–24 [Google Scholar]
  290. Leger B, Derave W, De Bock K, Hespel P, Russell AP. 290.  2008. Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Res. 11:163–75B [Google Scholar]
  291. Bigot A, Jacquemin V, Debacq-Chainiaux F, Butler-Browne GS, Toussaint O. 291.  et al. 2008. Replicative aging down-regulates the myogenic regulatory factors in human myoblasts. Biol. Cell 100:189–99 [Google Scholar]
  292. Pietrangelo T, Puglielli C, Mancinelli R, Beccafico S, Fano G, Fulle S. 292.  2009. Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation. Exp. Gerontol. 44:523–31 [Google Scholar]
  293. Beccafico S, Riuzzi F, Puglielli C, Mancinelli R, Fulle S. 293.  et al. 2011. Human muscle satellite cells show age-related differential expression of S100B protein and RAGE. Age 33:523–41 [Google Scholar]
  294. Vandenburgh H, Shansky J, Benesch-Lee F, Skelly K, Spinazzola JM. 294.  et al. 2009. Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts. FASEB J. 23:3325–34 [Google Scholar]
  295. Chamberlain JS, Rando TA. 295.  2006. Duchenne Muscular Dystrophy: Advances in Therapeutics New York: Taylor & Francis
  296. Langelaan ML, Boonen KJ, Rosaria-Chak KY, van der Schaft DW, Post MJ, Baaijens FP. 296.  2011. Advanced maturation by electrical stimulation: differences in response between C2C12 and primary muscle progenitor cells. J. Tissue Eng. Regen. Med. 5:529–39 [Google Scholar]
  297. Yuge L, Kataoka K. 297.  2000. Differentiation of myoblasts is accelerated in culture in a magnetic field. In Vitro Cell. Dev. Biol. Anim. 36:383–86 [Google Scholar]
  298. Goldspink G, Scutt A, Loughna PT, Wells DJ, Jaenicke T, Gerlach GF. 298.  1992. Gene expression in skeletal muscle in response to stretch and force generation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 262:R356–63 [Google Scholar]
  299. Powell CA, Smiley BL, Mills J, Vandenburgh HH. 299.  2002. Mechanical stimulation improves tissue-engineered human skeletal muscle. Am. J. Physiol. Cell Physiol. 283:C1557–65 [Google Scholar]
  300. Moon DG, Christ G, Stitzel JD, Atala A, Yoo JJ. 300.  2008. Cyclic mechanical preconditioning improves engineered muscle contraction. Tissue Eng. 14:848 [Google Scholar]
  301. Huang YC, Dennis RG, Baar K. 301.  2006. Cultured slow versus fast skeletal muscle cells differ in physiology and responsiveness to stimulation. Am. J. Physiol. Cell Physiol. 291:C11–17 [Google Scholar]
  302. Asano T, Ishizua T, Yawo H. 302.  2012. Optically controlled contraction of photosensitive skeletal muscle cells. Biotechnol. Bioeng. 109:199–204 [Google Scholar]
  303. Ahadian S, Ramón-Azcón J, Ostrovidov S, Camci-Unal G, Kaji H. 303.  et al. 2013. A contactless electrical stimulator: application to fabricate functional skeletal muscle tissue. Biomed. Microdevices 15:109–15 [Google Scholar]
  304. Harrison BC, Allen DL, Leinwand LA. 304.  2011. IIb or not IIb? Regulation of myosin heavy chain gene expression in mice and men. Skelet. Muscle 1:1–9 [Google Scholar]
  305. Jankowski R. 305.  2011. A comparison of commercially-available human skeletal muscle cells and media for research applications. Nat. Methods Appl. Notes. http://www.nature.com/app_notes/nmeth/2011/111406/full/an7998.html
  306. Owens J, Moreira K, Bain G. 306.  2013. Characterization of primary human skeletal muscle cells from multiple commercial sources. In Vitro Cell. Dev. Biol. Anim. 49:695–705 [Google Scholar]
  307. Fishman JM, Tyraskis A, Maghsoudlou P, Urbani L, Totonelli G. 307.  et al. 2013. Skeletal muscle tissue engineering: which cell to use. Tissue Eng. B 19:503–15 [Google Scholar]
  308. Zhu CH, Mouly V, Cooper RN, Mamchaoui K, Bigot A. 308.  et al. 2007. Cellular senescence in human myoblasts is overcome by human telomerase reverse transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and therapeutic strategies for muscular dystrophies. Aging Cell 6:515–23 [Google Scholar]
  309. Larkin LM, van der Meulen JH, Dennis RG, Kennedy JB. 309.  2006. Functional evaluation of nerve–skeletal muscle constructs engineered in vitro. In Vitro Cell. Dev. Biol. Anim. 42:75–82 [Google Scholar]
  310. Dhawan V, Lytle IF, Dow DE, Huang YC, Brown DL. 310.  2007. Neurotization improves contractile forces of tissue-engineered skeletal muscle. Tissue Eng. 13:2813–21 [Google Scholar]
  311. Das M, Rumsey JW, Bhargava N, Stancescu M, Hickman JJ. 311.  2009. Skeletal muscle tissue engineering: a maturation model promoting long-term survival of myotubes, structural development of the excitation-contraction coupling apparatus and neonatal myosin heavy chain expression. Biomaterials 30:5392–402 [Google Scholar]
  312. Das M, Rumsey JW, Bhargava N, Stancescu M, Hickman JJ. 312.  2010. A defined long-term in vitro tissue engineered model of neuromuscular junctions. Biomaterials 31:4880–88 [Google Scholar]
  313. Buller AJ, Eccles JC, Eccles RM. 313.  1960. Differentiation of fast and slow muscles in the cat hind limb. J. Physiol. 150:399–416 [Google Scholar]
  314. Bacou F, Rouanet P, Barjot C, Janmot C, Vigneron P, d'Albis A. 314.  1996. Expression of myosin isoforms in denervated, cross-reinnervated, and electrically stimulated rabbit muscles. Eur. J. Biochem. 236:539–47 [Google Scholar]
  315. Salmons S, Sreter FA. 315.  1976. Significance of impulse activity in the transformation of skeletal muscle type. Nature 263:30–34 [Google Scholar]
  316. 316. WHO (World Health Organ.) 2006. Neurological Disorders: Public Health Challenges. Geneva: WHO
  317. Herculano-Houzel S. 317.  2009. The human brain in numbers: a linearly scaled-up primate brain. Front. Hum. Neurosci. 3:31 [Google Scholar]
  318. Masland RH. 318.  2004. Neuronal cell types. Curr. Biol. 14:R497–500 [Google Scholar]
  319. Stevens CF. 319.  1998. Neuronal diversity: too many cell types for comfort. Curr. Biol. 8:R708–10 [Google Scholar]
  320. Gonzalez-Burgos G, Lewis DA. 320.  2012. NMDA receptor hypofunction, parvalbumin-positive neurons, and cortical gamma oscillations in schizophrenia. Schizophr. Bull. 38:950–57 [Google Scholar]
  321. Curley AA, Lewis DA. 321.  2012. Cortical basket cell dysfunction in schizophrenia. J. Physiol. 590:715–24 [Google Scholar]
  322. Samii A, Nutt JG, Ransom BR. 322.  2004. Parkinson's disease. Lancet 363:1783–93 [Google Scholar]
  323. DeMarse TB, Wagenaar DA, Blau AW, Potter SM. 323.  2001. The neurally controlled animat: biological brains acting with simulated bodies. Auton. Robots 11:305–10 [Google Scholar]
  324. DeMarse TB, Dockendorf KP. 324.  2005. Adaptive flight control with living neuronal networks on microelectrode arrays. Proc. Int. Joint Conf. Neural Netw. (IJCNN) 2005 31548–51 Piscataway, NJ: IEEE [Google Scholar]
  325. Novellino A, D'Angelo P, Cozzi L, Chiappalone M, Sanguineti V, Martinoia S. 325.  2007. Connecting neurons to a mobile robot: an in vitro bidirectional neural interface. Comput. Intell. Neurosci. 2007:12725 [Google Scholar]
  326. Abuelo D. 326.  2007. Microcephaly syndromes. Semin. Pediatr. Neurol. 14:118–27 [Google Scholar]
  327. Brustle O. 327.  2013. Developmental neuroscience: miniature human brains. Nature 501:319–20 [Google Scholar]
  328. Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS. 328.  et al. 2013. Cerebral organoids model human brain development and microcephaly. Nature 501:373–79 [Google Scholar]
  329. Jankovic J. 329.  2008. Parkinson's disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79:368–76 [Google Scholar]
  330. Xie HR, Hu LS, Li GY. 330.  2010. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chin. Med. J. 123:1086–92 [Google Scholar]
  331. Presgraves SP, Ahmed T, Borwege S, Joyce JN. 331.  2004. Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. Neurotox. Res. 5:579–98 [Google Scholar]
  332. Oyarce AM, Fleming PJ. 332.  1991. Multiple forms of human dopamine β-hydroxylase in SH-SY5Y neuroblastoma cells. Arch. Biochem. Biophys. 290:503–10 [Google Scholar]
  333. Wilson NR, Ty MT, Ingber DE, Sur M, Liu G. 333.  2007. Synaptic reorganization in scaled networks of controlled size. J. Neurosci. 27:13581–89 [Google Scholar]
  334. Peyrin JM, Deleglise B, Saias L, Vignes M, Gougis P. 334.  et al. 2011. Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers. Lab Chip 11:3663–73 [Google Scholar]
  335. Suter DM. 335.  2011. Live cell imaging of neuronal growth cone motility and guidance in vitro. Methods Mol. Biol. 769:65–86 [Google Scholar]
  336. Castellani RJ, Perry G. 336.  2014. The complexities of the pathology-pathogenesis relationship in Alzheimer disease. Biochem. Pharmacol. 88:671–76 [Google Scholar]
  337. Reitz C, Mayeux R. 337.  2014. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem. Pharmacol. 88:640–51 [Google Scholar]
  338. Agholme L, Lindstrom T, Kagedal K, Marcusson J, Hallbeck M. 338.  2010. An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. J. Alzheimer's Dis. 20:1069–82 [Google Scholar]
  339. Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira AI, Herland A. 339.  2014. A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials 35:1420–28 [Google Scholar]
  340. Franze K, Janmey PA, Guck J. 340.  2013. Mechanics in neuronal development and repair. Annu. Rev. Biomed. Eng. 15:227–51 [Google Scholar]
  341. Pasinelli P, Brown RH. 341.  2006. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci. 7:710–23 [Google Scholar]
  342. Phukan J, Pender NP, Hardiman O. 342.  2007. Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol. 6:994–1003 [Google Scholar]
  343. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H. 343.  et al. 2008. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218–21 [Google Scholar]
  344. Dunckley T, Huentelman MJ, Craig DW, Pearson JV, Szelinger S. 344.  et al. 2007. Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N. Engl. J. Med. 357:775–88 [Google Scholar]
  345. Aigner S, Heckel T, Zhang JD, Andreae LC, Jagasia R. 345.  2013. Human pluripotent stem cell models of autism spectrum disorder: emerging frontiers, opportunities, and challenges towards neuronal networks in a dish. Psychopharmacology 231:1089–104 [Google Scholar]
  346. Bauman ML, Kemper TL. 346.  2005. Neuroanatomic observations of the brain in autism: a review and future directions. Int. J. Dev. Neurosci. 23:183–87 [Google Scholar]
  347. Konopka G, Wexler E, Rosen E, Mukamel Z, Osborn GE. 347.  et al. 2012. Modeling the functional genomics of autism using human neurons. Mol. Psychiatry 17:202–14 [Google Scholar]
  348. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW. 348.  et al. 2010. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–39 [Google Scholar]
  349. Shcheglovitov A, Shcheglovitova O, Yazawa M, Portmann T, Shu R. 349.  et al. 2013. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 503:267–71 [Google Scholar]
  350. Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A. 350.  et al. 2011. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat. Med. 17:1657–62 [Google Scholar]
  351. Sheridan SD, Theriault KM, Reis SA, Zhou F, Madison JM. 351.  et al. 2011. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLOS ONE 6:e26203 [Google Scholar]
  352. Castren M, Tervonen T, Karkkainen V, Heinonen S, Castren E. 352.  et al. 2005. Altered differentiation of neural stem cells in fragile X syndrome. PNAS 102:17834–39 [Google Scholar]
  353. Brennand KJ, Simone A, Tran N, Gage FH. 353.  2012. Modeling psychiatric disorders at the cellular and network levels. Mol. Psychiatry 17:1239–53 [Google Scholar]
  354. Durnaoglu S, Genc S, Genc K. 354.  2011. Patient-specific pluripotent stem cells in neurological diseases. Stem Cells Int. 2011:212487 [Google Scholar]
  355. Fasano C, Kortleven C, Trudeau LE. 355.  2010. Chronic activation of the D2 autoreceptor inhibits both glutamate and dopamine synapse formation and alters the intrinsic properties of mesencephalic dopamine neurons in vitro. Eur. J. Neurosci. 32:1433–41 [Google Scholar]
  356. Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR. 356.  et al. 2011. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 480:547–51 [Google Scholar]
  357. Shi Y, Kirwan P, Smith J, Robinson HP, Livesey FJ. 357.  2012. Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat. Neurosci. 15:477–86 [Google Scholar]
  358. Penzes P, Buonanno A, Passafaro M, Sala C, Sweet RA. 358.  2013. Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders. J. Neurochem. 126:165–82 [Google Scholar]
  359. Thuret S, Moon LD, Gage FH. 359.  2006. Therapeutic interventions after spinal cord injury. Nat. Rev. Neurosci. 7:628–43 [Google Scholar]
  360. Abu-Rub M, McMahon S, Zeugolis DI, Windebank A, Pandit A. 360.  2010. Spinal cord injury in vitro: modelling axon growth inhibition. Drug Discov. Today 15:436–43 [Google Scholar]
  361. Zimmermann DR, Dours-Zimmermann MT. 361.  2008. Extracellular matrix of the central nervous system: from neglect to challenge. Histochem. Cell Biol. 130:635–53 [Google Scholar]
  362. Lau LW, Cua R, Keough MB, Haylock-Jacobs S, Yong VW. 362.  2013. Pathophysiology of the brain extracellular matrix: a new target for remyelination. Nat. Rev. Neurosci. 14:722–29 [Google Scholar]
  363. Gilbert RJ, McKeon RJ, Darr A, Calabro A, Hascall VC, Bellamkonda RV. 363.  2005. CS-4,6 is differentially up-regulated in glial scar and is a potent inhibitor of neurite extension. Mol. Cell. Neurosci. 29:545–58 [Google Scholar]
  364. Cullen DK, Stabenfeldt SE, Simon CM, Tate CC, LaPlaca MC. 364.  2007. In vitro neural injury model for optimization of tissue-engineered constructs. J. Neurosci. Res. 85:3642–51 [Google Scholar]
  365. East E, Golding JP, Phillips JB. 365.  2009. A versatile 3D culture model facilitates monitoring of astrocytes undergoing reactive gliosis. J. Tissue Eng. Regen. Med. 3:634–46 [Google Scholar]
  366. Smyth AM, Lawrie SM. 366.  2013. The neuroimmunology of schizophrenia. Clin. Psychopharmacol. Neurosci. 11:107–11 [Google Scholar]
  367. Roussos P, Haroutunian V. 367.  2014. Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities. Front. Cell. Neurosci. 8:5 [Google Scholar]
  368. Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S. 368.  et al. 2011. Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9:113–18 [Google Scholar]
  369. Brennand KJ, Gage FH. 369.  2012. Modeling psychiatric disorders through reprogramming. Dis. Models Mech. 5:26–32 [Google Scholar]
  370. Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T. 370.  et al. 2011. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476:228–31 [Google Scholar]
  371. Tran NN, Ladran IG, Brennand KJ. 371.  2013. Modeling schizophrenia using induced pluripotent stem cell–derived and fibroblast-induced neurons. Schizophr. Bull. 39:4–10 [Google Scholar]
  372. Paulsen BdS, da Silveira MS, Galina A, Rehen SK. 372.  2013. Pluripotent stem cells as a model to study oxygen metabolism in neurogenesis and neurodevelopmental disorders. Arch. Biochem. Biophys. 534:3–10 [Google Scholar]
  373. Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS. 373.  et al. 2013. Structural and molecular interrogation of intact biological systems. Nature 497:332–37 [Google Scholar]
  374. Park J, Koito H, Li J, Han A. 374.  2009. Microfluidic compartmentalized co-culture platform for CNS axon myelination research. Biomed. Microdevices 11:1145–53 [Google Scholar]
  375. Brannvall K, Bergman K, Wallenquist U, Svahn S, Bowden T. 375.  et al. 2007. Enhanced neuronal differentiation in a three-dimensional collagen-hyaluronan matrix. J. Neurosci. Res. 85:2138–46 [Google Scholar]
  376. Kato-Negishi M, Morimoto Y, Onoe H, Takeuchi S. 376.  2013. Millimeter-sized neural building blocks for 3D heterogeneous neural network assembly. Adv. Healthc. Mater. 2:1564–70 [Google Scholar]
  377. Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR. 377.  et al. 2010. MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis Rheum. 62:1361–71 [Google Scholar]
  378. Blasioli DJ, Matthews GL, Kaplan DL. 378.  2014. The degradation of chondrogenic pellets using co-cultures of synovial fibroblasts and U937 cells. Biomaterials 35:1185–91 [Google Scholar]
  379. Sun L, Wang X, Kaplan DL. 379.  2011. A 3D cartilage–inflammatory cell culture system for the modeling of human osteoarthritis. Biomaterials 32:5581–89 [Google Scholar]
  380. Cortial D, Gouttenoire J, Rousseau CF, Ronziere MC, Piccardi N. 380.  et al. 2006. Activation by IL-1 of bovine articular chondrocytes in culture within a 3D collagen-based scaffold. An in vitro model to address the effect of compounds with therapeutic potential in osteoarthritis. Osteoarthr. Cartil. 14:631–40 [Google Scholar]
  381. Towle CA, Hung HH, Bonassar LJ, Treadwell BV, Mangham DC. 381.  1997. Detection of interleukin-1 in the cartilage of patients with osteoarthritis: a possible autocrine/paracrine role in pathogenesis. Osteoarthr. Cartil. 5:293–300 [Google Scholar]
  382. Pol A, Bergers M, van Ruissen F, Pfundt R, Schalkwijk J. 382.  2002. A simple technique for high-throughput screening of drugs that modulate normal and psoriasis-like differentiation in cultured human keratinocytes. Skin Pharmacol. Appl. Skin Physiol. 15:252–61 [Google Scholar]
  383. Pol A, Bergers M, Schalkwijk J. 383.  2003. Comparison of antiproliferative effects of experimental and established antipsoriatic drugs on human keratinocytes, using a simple 96-well-plate assay. In Vitro Cell. Dev. Biol. Anim. 39:36–42 [Google Scholar]
  384. Amigo M, Schalkwijk J, Olthuis D, De Rosa S, Paya M. 384.  et al. 2006. Identification of avarol derivatives as potential antipsoriatic drugs using an in vitro model for keratinocyte growth and differentiation. Life Sci. 79:2395–404 [Google Scholar]
  385. van den Bogaard EH, Tjabringa GS, Joosten I, Vonk-Bergers M, van Rijssen E. 385.  et al. 2014. Crosstalk between keratinocytes and T cells in a 3D microenvironment: a model to study inflammatory skin diseases. J. Investig. Dermatol. 134:719–27 [Google Scholar]
  386. Villenave R, Thavagnanam S, Sarlang S, Parker J, Douglas I. 386.  et al. 2012. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. PNAS 109:5040–45 [Google Scholar]
  387. Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD. 387.  2004. Human and avian influenza viruses target different cell types in cultures of human airway epithelium. PNAS 101:4620–24 [Google Scholar]
  388. Ludlow M, Rennick LJ, Sarlang S, Skibinski G, McQuaid S. 388.  et al. 2010. Wild-type measles virus infection of primary epithelial cells occurs via the basolateral surface without syncytium formation or release of infectious virus. J. Gen. Virol. 91:971–79 [Google Scholar]
  389. Sims AC, Burkett SE, Yount B, Pickles RJ. 389.  2008. SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium. Virus Res. 133:33–44 [Google Scholar]
  390. Zhang L, Bukreyev A, Thompson CI, Watson B, Peeples ME. 390.  et al. 2005. Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J. Virol. 79:1113–24 [Google Scholar]
  391. Bermudez LE. 391.  2002. The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infect. Immun. 70:140–46 [Google Scholar]
  392. Bhat P, Snooks MJ, Anderson DA. 392.  2011. Hepatocytes traffic and export hepatitis B virus basolaterally by polarity-dependent mechanisms. J. Virol. 85:12474–81 [Google Scholar]
  393. Ren D, Nelson KL, Uchakin PN, Smith AL, Gu XX. 393.  et al. 2012. Characterization of extended co-culture of non-typeable Haemophilus influenzae with primary human respiratory tissues. Exp. Biol. Med. 237:540–47 [Google Scholar]
  394. Lamers RP, Eade CR, Waring AJ, Cole AL, Cole AM. 394.  2011. Characterization of the retrocyclin analogue RC-101 as a preventative of Staphylococcus aureus nasal colonization. Antimicrob. Agents Chemother. 55:5338–46 [Google Scholar]
  395. Carterson AJ, Höner zu Bentrup K, Ott CM, Clarke MS, Pierson DL. 395.  et al. 2005. A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis. Infect. Immun. 73:1129–40 [Google Scholar]
  396. Smith YC, Grande KK, Rasmussen SB, O'Brien AD. 396.  2006. Novel three-dimensional organoid model for evaluation of the interaction of uropathogenic Escherichia coli with terminally differentiated human urothelial cells. Infect. Immun. 74:750–57 [Google Scholar]
  397. Cimetta E, Franzoso M, Trevisan M, Serena E, Zambon A. 397.  et al. 2012. Microfluidic-driven viral infection on cell cultures: theoretical and experimental study. Biomicrofluidics 6:24127–712 [Google Scholar]
  398. Zhu Y, Warrick JW, Haubert K, Beebe DJ, Yin J. 398.  2009. Infection on a chip: a microscale platform for simple and sensitive cell-based virus assays. Biomed. Microdevices 11:565–70 [Google Scholar]
  399. Walker G. 399.  2004. Cell infection within a microfluidic device using virus gradients. Sens. Actuators B 98:347–55 [Google Scholar]
  400. Shelby JP, White J, Ganesan K, Rathod PK, Chiu DT. 400.  2003. A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum–infected erythrocytes. PNAS 100:14618–22 [Google Scholar]
  401. Handayani S, Chiu DT, Tjitra E, Kuo JS, Lampah D. 401.  et al. 2009. High deformability of Plasmodium vivax–infected red blood cells under microfluidic conditions. J. Infect. Dis. 199:445–50 [Google Scholar]
  402. Antia M, Herricks T, Rathod PK. 402.  2007. Microfluidic modeling of cell-cell interactions in malaria pathogenesis. PLOS Pathog. 3:e99 [Google Scholar]
  403. Mishra DK, Sakamoto JH, Thrall MJ, Baird BN, Blackmon SH. 403.  et al. 2012. Human lung cancer cells grown in an ex vivo 3D lung model produce matrix metalloproteinases not produced in 2D culture. PLOS ONE 7:e45308 [Google Scholar]
  404. Hsu TH, Xiao JL, Tsao YW, Kao YL, Huang SH. 404.  et al. 2011. Analysis of the paracrine loop between cancer cells and fibroblasts using a microfluidic chip. Lab Chip 11:1808–14 [Google Scholar]
  405. Chen YA, King AD, Shih HC, Peng CC, Wu CY. 405.  et al. 2011. Generation of oxygen gradients in microfluidic devices for cell culture using spatially confined chemical reactions. Lab Chip 11:3626–33 [Google Scholar]
  406. Mehta G, Hsiao AY, Ingram M, Luker GD, Takayama S. 406.  2012. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J. Control. Release 164:92–204 [Google Scholar]
  407. Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS. 407.  2002. The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111:29–40 [Google Scholar]
  408. Kenny PA, Lee GY, Myers CA, Neve RM, Semeiks JR. 408.  et al. 2007. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol. Oncol. 1:84–96 [Google Scholar]
  409. Brock A, Krause S, Li H, Kowalski M, Goldberg MS. 409.  et al. 2014. Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice. Sci. Transl. Med. 6:217ra2 [Google Scholar]
  410. White DE, Kurpios NA, Zuo D. 410.  et al. 2004. Targeted disruption of β1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction. Cancer Cell 6:159–70 [Google Scholar]
  411. Bissell MJ, Weaver VM, Lelievre SA. 411.  et al. 1999. Tissue structure, nuclear organization, and gene expression in normal and malignant breast. Cancer Res. 59:1757s–63s discussion 1763s–64s [Google Scholar]
  412. Weaver VM, Petersen OW, Wang F. 412.  et al. 1997. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J. Cell Biol. 137:231–45 [Google Scholar]
  413. Park CC, Zhang H, Pallavicini M, Gray JW, Baehner F. 413.  et al. 2006. β1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Res. 66:1526–35 [Google Scholar]
  414. Bischof AG, Yüksel D, Mammoto T, Mammoto A, Krause S, Ingber DE. 414.  2013. Breast cancer normalization induced by embryonic mesenchyme is mediated by extracellular matrix biglycan. Integr. Biol. 5:1045–56 [Google Scholar]
  415. Sung KE, Yang N, Pehlke C, Keely PJ, Eliceiri KW. 415.  et al. 2011. Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects. Integr. Biol. 3:439–50 [Google Scholar]
  416. Huang CP, Lu J, Seon H, Lee AP, Flanagan L. 416.  et al. 2009. Engineering microscale cellular niches for three-dimensional multicellular co-cultures. Lab Chip 9:1740–48 [Google Scholar]
  417. Kim S, Lee H, Chung M, Jeon NL. 417.  2013. Engineering of functional, perfusable 3D microvascular networks on a chip. Lab Chip 13:1489–500 [Google Scholar]
  418. Walsh CL, Babin BM, Kasinskas RW, Foster JA, McGarry MJ, Forbes NS. 418.  2009. A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics. Lab Chip 9545–54
  419. Leung M, Kievit FM, Florczyk SJ, Veiseh O, Wu J. 419.  et al. 2010. Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance. Pharm. Res. 27:1939–48 [Google Scholar]
  420. Cheng S, Prot JM, Leclerc E, Bois FY. 420.  2012. Zonation related function and ubiquitination regulation in human hepatocellular carcinoma cells in dynamic versus static culture conditions. BMC Genomics 13:54 [Google Scholar]
  421. Yates C, Shepard CR, Papworth G, Dash A, Stolz DB. 421.  et al. 2007. Novel three-dimensional organotypic liver bioreactor to directly visualize early events in metastatic progression. Adv. Cancer Res. 97:225–46 [Google Scholar]
  422. Wheeler SE, Borenstein JT, Clark AM, Ebrahimkhani MR, Fox IJ. 422.  et al. 2013. All-human microphysical model of metastasis therapy. Stem Cell Res. Ther. 4:Suppl. 1S11 [Google Scholar]
  423. Abe M. 423.  2011. Targeting the interplay between myeloma cells and the bone marrow microenvironment in myeloma. Int. J. Hematol. 94:334–43 [Google Scholar]
  424. Kirshner J, Thulien KJ, Martin LD, Marun CD, Reiman T. 424.  et al. 2008. A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma. Blood 112:2935–45 [Google Scholar]
  425. Zhang W, Lee WY, Siegel DS, Tolias P, Zilberberg J. 425.  2014. Patient-specific 3D microfluidic tissue model for multiple myeloma. Tissue Eng. C 20:663–70 [Google Scholar]
  426. Hou L, Liu T, Tan J, Meng W, Deng L. 426.  et al. 2009. Long-term culture of leukemic bone marrow primary cells in biomimetic osteoblast niche. Int. J. Hematol. 90:281–91 [Google Scholar]
  427. Blanco TM, Mantalaris A, Bismarck A, Panoskaltsis N. 427.  2010. The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukemia. Biomaterials 31:2243–51 [Google Scholar]
  428. Aljitawi OS, Li D, Xiao Y, Zhang D, Ramachandran K. 428.  et al. 2014. A novel three-dimensional stromal-based model for in vitro chemotherapy sensitivity testing of leukemia cells. Leuk. Lymphoma 55:378–91 [Google Scholar]
  429. Baker BM, Trappmann B, Stapleton SC, Toro E, Chen CS. 429.  2013. Microfluidics embedded within extracellular matrix to define vascular architectures and pattern diffusive gradients. Lab Chip. 13:3246–52 [Google Scholar]
  430. Nguyen DHT, Stapleton SC, Yang MT, Cha SS, Choi CK. 430.  et al. 2013. Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. PNAS 110:6712–17 [Google Scholar]
  431. Chen MB, Whisler JA, Jeon JS, Kamm RD. 431.  2013. Mechanisms of tumor cell extravasation in an in vitro microvascular network platform. Integr. Biol. 5:1262–71 [Google Scholar]
  432. Moya ML, Hsu YH, Lee AP, Hughes CC, George SC. 432.  2013. In vitro perfused human capillary networks. Tissue Eng. 19:730–37 [Google Scholar]
  433. Bischel LL, Young EW, Mader BR, Beebe DJ. 433.  2013. Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials 34:1471–77 [Google Scholar]
  434. Hsu YH, Moya ML, Hughes CC, George SC, Lee AP. 434.  2013. A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays. Lab Chip 13:2990–98 [Google Scholar]
  435. Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. 435.  2012. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. PNAS 109:13515–20 [Google Scholar]
  436. Chaw KC, Manimaran M, Tay EH, Swaminathan S. 436.  2007. Multi-step microfluidic device for studying cancer metastasis. Lab Chip 7:1041–47 [Google Scholar]
  437. Song JW, Cavnar SP, Walker AC, Luker KE, Gupta M. 437.  et al. 2009. Microfluidic endothelium for studying the intravascular adhesion of metastatic breast cancer cells. PLOS ONE 4:5756 [Google Scholar]
  438. Bersini S, Jeon JS, Dubini G, Arrigoni C, Chung S. 438.  et al. 2014. A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone. Biomaterials 35:2454–61 [Google Scholar]
  439. Mastro AM, Vogler EA. 439.  2009. A three-dimensional osteogenic tissue model for the study of metastatic tumor cell interactions with bone. Cancer Res. 69:4097–100 [Google Scholar]
  440. Talukdar S, Kundu SC. 440.  2013. Engineered 3D silk-based metastasis models: interactions between human breast adenocarcinoma, mesenchymal stem cells and osteoblast-like cells. Adv. Funct. Mater. 23:5249–60 [Google Scholar]
  441. Krishnan V, Vogler EA, Sosnoski DM, Mastro AM. 441.  2014. In vitro mimics of bone remodeling and the vicious cycle of cancer in bone. J. Cell. Physiol. 229:453–62 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article