A biologically inspired lung-on-a-chip device for the study of protein-induced lung inflammation.

This study reports a biomimetic microsystem that reconstitutes the lung microenvironment for monitoring the role of eosinophil cationic protein (ECP) in lung inflammation. ECP induces the airway epithelial cell expression of CXCL-12, which in turn stimulates the migration of fibrocytes towards the epithelium. This two-layered microfluidic system provides a feasible platform for perfusion culture, and was used in this study to reveal that the CXCL12-CXCR4 axis mediates ECP induced fibrocyte extravasation in lung inflammation. This 'lung-on-a-chip' microdevice serves as a dynamic transwell system by introducing a flow that can reconstitute the blood vessel-tissue interface for in vitro assays, enhancing pre-clinical studies. We made an attempt to develop a new microfluidic model which could not only simulate the transwell for studying cell migration, but could also study the migration in the presence of a flow mimicking the physiological conditions in the body. As blood vessels are the integral part of our body, this model gives an opportunity to study more realistic in vitro models of organs where the blood vessel i.e. flow based migration is involved.

[1]  Holger Gerhardt,et al.  Tissue engineering: Blood vessels on a chip , 2012, Nature.

[2]  D. Knight.  Epithelium–fibroblast interactions in response to airway inflammation , 2001, Immunology and cell biology.

[3]  Donald E Ingber,et al.  Microengineered physiological biomimicry: organs-on-chips. , 2012, Lab on a chip.

[4]  M. D. Chang,et al.  TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B Cells , 2010, BMC Cell Biology.

[5]  G. Gleich.  Mechanisms of eosinophil-associated inflammation. , 2000, The Journal of allergy and clinical immunology.

[6]  N. Krug,et al.  Eosinophil cationic protein alters pulmonary surfactant structure and function in asthma. , 2004, The Journal of allergy and clinical immunology.

[7]  C. Brightling,et al.  The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. , 2005, American journal of respiratory and critical care medicine.

[8]  Jong Hwan Sung,et al.  Microtechnology for Mimicking In Vivo Tissue Environment , 2012, Annals of Biomedical Engineering.

[9]  Sang-Hoon Lee,et al.  Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects. , 2013, Lab on a chip.

[10]  A. Berg,et al.  BBB ON CHIP: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function , 2013, Biomedical microdevices.

[11]  C. Brightling,et al.  Fibrocyte localization to the airway smooth muscle is a feature of asthma. , 2009, The Journal of allergy and clinical immunology.

[12]  K. Chung,et al.  Increased circulating fibrocytes in asthma with chronic airflow obstruction. , 2008, American journal of respiratory and critical care medicine.

[13]  Takehiko Kitamori,et al.  Development of an osteoblast-based 3D continuous-perfusion microfluidic system for drug screening , 2008, Analytical and bioanalytical chemistry.

[14]  J. Bousquet,et al.  Eosinophilic inflammation in asthma. , 1990, The New England journal of medicine.

[15]  J. Wilson,et al.  Assessing the evidence for remodelling of the airway in asthma. , 2001, Pulmonary pharmacology & therapeutics.

[16]  Donald E Ingber,et al.  Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[17]  M. Burdick,et al.  Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. , 2004, The Journal of clinical investigation.

[18]  D. Ingber,et al.  Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[19]  S. Orkin,et al.  A Critical Role for Eosinophils in Allergic Airways Remodeling , 2004, Science.

[20]  D. Ingber,et al.  Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. , 2012, Lab on a chip.

[21]  M. Gillette,et al.  New perspectives on neuronal development via microfluidic environments , 2012, Trends in Neurosciences.

[22]  C. Corrigan.  Mechanisms of asthma , 2008 .

[23]  Cheng-Hsien Liu,et al.  Rapid heterogeneous liver-cell on-chip patterning via the enhanced field-induced dielectrophoresis trap. , 2006, Lab on a chip.

[24]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[25]  Hong Peng,et al.  Fibrocytes: emerging effector cells in chronic inflammation. , 2012, Current opinion in pharmacology.

[26]  A. Berg,et al.  Organs-on-chips: breaking the in vitro impasse. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[27]  Chih,et al.  TNF-alpha Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2 B Cells , 2010 .

[28]  Yu-Hsiang Hsu,et al.  In vitro perfused human capillary networks. , 2013, Tissue engineering. Part C, Methods.

[29]  J Emnéus,et al.  Modular microfluidic system as a model of cystic fibrosis airways. , 2012, Biomicrofluidics.

[30]  P. Bradding,et al.  Chemokines and their receptors as potential targets for the treatment of asthma , 2007, British journal of pharmacology.

[31]  S. Giselbrecht,et al.  Promotion of osteoblast differentiation in 3D biomaterial micro-chip arrays comprising fibronectin-coated poly(methyl methacrylate) polycarbonate. , 2011, Biomaterials.

[32]  Laurent Griscom,et al.  Development of a Renal Microchip for In Vitro Distal Tubule Models , 2007, Biotechnology progress.

[33]  Michael L. Shuler,et al.  Growth of endothelial cells on microfabricated silicon nitride membranes for anin vitro model of the blood-brain barrier , 2003 .

[34]  Cheng-Hsien Liu,et al.  Liver-cell patterning lab chip: mimicking the morphology of liver lobule tissue. , 2013, Lab on a chip.

[35]  R. Strieter,et al.  The role of CXC chemokines in pulmonary fibrosis. , 2007, The Journal of clinical investigation.

[36]  A. Malmström,et al.  Tissue fibrocytes in patients with mild asthma: A possible link to thickness of reticular basement membrane? , 2006, Respiratory research.