Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Lung on a Chip for Drug Screening and Design

Author(s): Ahmet Akif Kızılkurtlu, Tuğçe Polat, Gül Banu Aydın and Ali Akpek*

Volume 24, Issue 45, 2018

Page: [5386 - 5396] Pages: 11

DOI: 10.2174/1381612825666190208122204

Price: $65

Abstract

Lung-on-a-chip is a micro device that combines the techniques of bioengineering, microbiology, polymer science and microfluidics disciplines in order to mimic physicochemical features and microenvironments, multicellular constructions, cell-cell interfaces of a human lung. Specifically, most novel lung on a chip designs consist of two micro-channeled outer parts, flexible and porous Polydimethylsiloxane (PDMS) membrane to create separation of air-blood chamber and subsidiary vacuum channels which enable stretching of the PDMS membrane to mimic movement mechanisms of the lung. Therefore, studies aim to emulate both tissue and organ functionality since it shall be creating great potential for advancing the studies about drug discovery, disease etiology and organ physiology compared with 2D (two dimensional) and 3D (three dimensional) cell culture models and current organoids. In this study, history of researches on lung anatomy and physiology, techniques of recreating lung functionality such as cell cultures in 2D and 3D models, organoids were covered and finally most advanced and recent state of the art technology product lung-on-a-chips’ construction steps, advantages compared with other techniques, usage in lung modeling and diseases, present and future offers were analyzed in detail.

Keywords: Lung-on-a-chip, organ-on-a-chip, microfluidics, lung models, lung, micro engineering.

[1]
Effros RM. Anatomy, development, and physiology of the lungs. GI Motility online. 2006.
[2]
Rizzo DC. Fundamentals of anatomy and physiology. 2015.
[3]
Marieb EN, Hoehn K. Human anatomy & physiology 2007.
[4]
Structure Of Lungs And Esopha. 2017. Available from. http://pluspng.com/png-120855.html
[5]
Adler S, Basketter D, Creton S, et al. Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010. Arch Toxicol 2011; 85(5): 367-485.
[6]
Kleinert M, Clemmensen C, Hofmann SM, et al. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol 2018; 14(3): 140-62.
[7]
Bonfield TL. In vivo models of lung disease. Lung Diseases-Selected State of the Art Reviews 2012.
[8]
Ragaller M, Richter T. Acute lung injury and acute respiratory distress syndrome. J Emerg Trauma Shock 2010; 3(1): 43-51.
[9]
Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med 1967; 276(7): 357-68.
[10]
Snider GL. Interstitial pulmonary fibrosis. Chest 1986; 89(3)(Suppl.): 115S-21S.
[11]
Djukanović R, Wilson JW, Britten KM, et al. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis 1992; 145(3): 669-74.
[12]
Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997; 111(6): 1710-7.
[13]
Davies JC, Alton EWFW, Bush A. Cystic fibrosis. BMJ 2007; 335(7632): 1255-9.
[14]
Simonetti G, Bertilaccio MT, Ghia P, Klein U, et al. Mouse models in the study of chronic lymphocytic leukemia pathogenesis and therapy. Blood 2014; 124(7): 1010-9.
[15]
Villa-Diaz LG, Ross AM, Lahann J, Krebsbach PH. Concise review: The evolution of human pluripotent stem cell culture: from feeder cells to synthetic coatings. Stem Cells 2013; 31(1): 1-7.
[16]
Duval K, Grover H, Han LH, et al. Modeling Physiological Events in 2D vs. 3D Cell Culture. Physiology 2017; 32(4): 266-77.
[17]
Biospectrumindia. Lonza enriches its Cell-Culture techniques with Quasi Vivo System. 2018, February 13; Available from. https://www.biospectrumindia.com/news/43/10390/lonza-enriches-its-cell-culture-techniques-with-quasi-vivo-system.html
[18]
Fang Y, Eglen RM. Three-dimensional cell cultures in drug discovery and development Slas discovery: Advancing Life Sciences R&D, 2017. 22(5): p. 456-472.
[19]
Amann A, Zwierzina M, Gamerith G, et al. Development of an innovative 3D cell culture system to study tumour-stroma interactions in non-small cell lung cancer cells. PLoS One 2014; 9(3): e92511.
[20]
Chimenti I, Pagano F, Angelini F, et al. Human lung spheroids as in vitro niches of lung progenitor cells with distinctive paracrine and plasticity properties. Stem Cells Transl Med 2017; 6(3): 767-77.
[21]
Horváth L, Umehara Y, Jud C, Blank F, Petri-Fink A, Rothen-Rutishauser B. Engineering an in vitro air-blood barrier by 3D bioprinting. Scientific reports 2015; 5: srep07974.
[22]
Wüst S, Müller R, Hofmann S. Controlled positioning of cells in biomaterials-approaches towards 3D tissue printing. J Funct Biomater 2011; 2(3): 119-54.
[23]
Gao G, Huang Y, Schilling AF, Hubbell K, Cui X. Organ Bioprinting: Are We There Yet? Adv Healthc Mater 2018; 7(1): 1701018.
[24]
Kolesky DB, Homan KA, Skylar-Scott MA, Lewis JA. Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci USA 2016; 113(12): 3179-84.
[25]
Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol 2014; 32(8): 773-85.
[26]
Lee D-H, Bae CY, Kwon S, Park J. User-friendly 3D bioassays with cell-containing hydrogel modules: Narrowing the gap between microfluidic bioassays and clinical end-users’ needs. Lab Chip 2015; 15(11): 2379-87.
[27]
Ozbolat I. 3D Bioprinting: Fundamentals 2016.
[28]
Yang X, Li K, Zhang X, et al. Nanofiber membrane supported lung-on-a-chip microdevice for anti-cancer drug testing. Lab Chip 2018; 18(3): 486-95.
[29]
Ellem SJ, De-Juan-Pardo EM, Risbridger GP. In vitro modeling of the prostate cancer microenvironment. Adv Drug Deliv Rev 2014; 79-80: 214-21.
[30]
Asghar W, El Assal R, Shafiee H, Pitteri S, Paulmurugan R, Demirci U. Engineering cancer microenvironments for in vitro 3-D tumor models. Mater Today (Kidlington) 2015; 18(10): 539-53.
[31]
Wu Z, Su X, Xu Y, Kong B, Sun W, Mi S. Bioprinting three-dimensional cell-laden tissue constructs with controllable degradation. Sci Rep 2016; 6: 24474.
[32]
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010; 328(5986): 1662-8.
[33]
Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol 2014; 32(8): 760-72.
[34]
Delgado O, Kaisani AA, Spinola M, et al. Multipotent capacity of immortalized human bronchial epithelial cells. PLoS One 2011; 6(7): e22023.
[35]
Coraux C, Nawrocki-Raby B, Hinnrasky J, et al. Embryonic stem cells generate airway epithelial tissue. Am J Respir Cell Mol Biol 2005; 32(2): 87-92.
[36]
Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL. Lung organoids: current uses and future promise. Development 2017; 144(6): 986-97.
[37]
Hogan BL, Barkauskas CE, Chapman HA, et al. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell 2014; 15(2): 123-38.
[38]
Rock JR, Onaitis MW, Rawlins EL, et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci USA 2009; 106(31): 12771-5.
[39]
Nikolić MZ, Caritg O, Jeng Q, et al. Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids. eLife 2017; 6: 6.
[40]
Lee J-H, Bhang DH, Beede A, et al. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 2014; 156(3): 440-55.
[41]
Dye BR, Dedhia PH, Miller AJ, et al. A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. eLife 2016; 5: 5.
[42]
Nadkarni RR, Abed S, Draper JS. Organoids as a model system for studying human lung development and disease. Biochem Biophys Res Commun 2016; 473(3): 675-82.
[43]
Benam KH, Villenave R, Lucchesi C, et al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods 2016; 13(2): 151-7.
[44]
Dye BR, Hill DR, Ferguson MA, et al. In vitro generation of human pluripotent stem cell derived lung organoids. eLife 2015; 4: 4.
[45]
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010; 328(5986): 1662-8.
[46]
Selimović S, Dokmeci MR, Khademhosseini A. Organs-on-a-chip for drug discovery. Curr Opin Pharmacol 2013; 13(5): 829-33.
[47]
Zhang Y, Gazit Z, Pelled G, Gazit D, Vunjak-Novakovic G. Patterning osteogenesis by inducible gene expression in microfluidic culture systems. Integr Biol 2011; 3(1): 39-47.
[48]
Jang K-J, Suh K-Y. A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip 2010; 10(1): 36-42.
[49]
van der Meer AD, Orlova VV, ten Dijke P, van den Berg A, Mummery CL. Three-dimensional co-cultures of human endothelial cells and embryonic stem cell-derived pericytes inside a microfluidic device. Lab Chip 2013; 13(18): 3562-8.
[50]
Jang K-J, Mehr AP, Hamilton GA, et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol 2013; 5(9): 1119-29.
[51]
Esch MB, Sung JH, Yang J, et al. On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic ‘body-on-a-chip’ devices. Biomed Microdevices 2012; 14(5): 895-906.
[52]
Xiao R-R, Zeng WJ, Li YT, et al. Simultaneous generation of gradients with gradually changed slope in a microfluidic device for quantifying axon response. Anal Chem 2013; 85(16): 7842-50.
[53]
Torisawa YS, Spina CS, Mammoto T, et al. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat Methods 2014; 11(6): 663-9.
[54]
Booth R, Kim H. Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB). Lab Chip 2012; 12(10): 1784-92.
[55]
Grosberg A, Nesmith AP, Goss JA, Brigham MD, McCain ML, Parker KK. Muscle on a chip: in vitro contractility assays for smooth and striated muscle. J Pharmacol Toxicol Methods 2012; 65(3): 126-35.
[56]
Musah S, Mammoto A, Ferranate TC, et al. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip Nat Biomed Eng; 2017: 1(5): 0069.
[57]
Medicine Fo. Human Organs On Chips 2016.https://www.youtube.com/watch?v=0jf6Tor9WtA
[58]
Nagrath S, Sequist LV, Maheswaran S, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 2007; 450(7173): 1235-9.
[59]
Siyan W, Feng Y, Lichuan Z, et al. Application of microfluidic gradient chip in the analysis of lung cancer chemotherapy resistance. J Pharm Biomed Anal 2009; 49(3): 806-10.
[60]
Stott SL, Hsu CH, Tsukrov DI, et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci USA 2010; 107(43): 18392-7.
[61]
Xu Z, Gao Y, Hao Y, et al. Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials 2013; 34(16): 4109-17.
[62]
Huang T, Jia CP. Jun-Yang , et al Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip. Biosens Bioelectron 2014; 51: 213-8.
[63]
Earhart CM, Hughes CE, Gaster RS, et al. Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips. Lab Chip 2014; 14(1): 78-88.
[64]
McDonald JC, Whitesides GM. Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc Chem Res 2002; 35(7): 491-9.
[65]
Ochs M, Mühlfeld C. Quantitative microscopy of the lung: a problem-based approach. Part 1: basic principles of lung stereology. Am J Physiol Lung Cell Mol Physiol 2013; 305(1): L15-22.
[66]
Ball JM, James RD. Fine phase mixtures as minimizers of energy. Arch Ration Mech Anal 1987; 100(1): 13-52.
[67]
Huh DD. A human breathing lung-on-a-chip. Ann Am Thorac Soc 2015; 12(Suppl. 1): S42-4.
[68]
Mauriac H. Organs On Chip 2017. 2017; Available from https://www.elveflow.com/organs-on-chip/organs-chip-review/
[69]
Huh D, et al. A human disease model of drug toxicity–induced pulmonary edema in a lung-on-a-chip microdevice. Science translational medicine 2012; 4(159): 159-47.
[70]
Long C, Finch C, Esch M, Anderson W, Shuler M, Hickman J. Design optimization of liquid-phase flow patterns for microfabricated lung on a chip. Ann Biomed Eng 2012; 40(6): 1255-67.
[71]
Punde TH, Wu WH, Lien PC, et al. A biologically inspired lung-on-a-chip device for the study of protein-induced lung inflammation. Integr Biol 2015; 7(2): 162-9.
[72]
Stucki AO, Stucki JD, Hall SR, et al. A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Lab Chip 2015; 15(5): 1302-10.
[73]
Wang L, Tao T, Su W, Yu H, Yu Y, Qin J. A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice. Lab Chip 2017; 17(10): 1749-60.
[74]
Griffin M, Bhandari R, Hamilton G, Chan YC, Powell JT. Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen. J Cell Sci 1993; 105(Pt 2): 423-32.
[75]
Shannon JM, Pan T, Nielsen LD, Edeen KE, Mason RJ. Lung fibroblasts improve differentiation of rat type II cells in primary culture. Am J Respir Cell Mol Biol 2001; 24(3): 235-44.
[76]
Herold S, Mayer K, Lohmeyer J. Acute lung injury: how macrophages orchestrate resolution of inflammation and tissue repair. Front Immunol 2011; 2: 65.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy