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Strategic grant

Developing a platform of in vitro models of asthmatic and healthy lung: an alternative to the use of animals in asthma research

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At a glance

Completed
Award date
February 2011 - December 2013
Grant amount
£499,467
Principal investigator
Dr Felicity Rose

Co-investigator(s)

Institute
University of Nottingham

R

  • Replacement

Contents

Application abstract

Asthma is a complex inflammatory disease of the lungs. Despite new treatments for asthma sufferers constantly being developed, not all patients respond well and asthma related deaths remain high (one every 19 minutes) and 20 million working days are lost each year in the UK alone. The only way to improve treatments for those suffering with severe asthma and to reduce the number of associated deaths is to understand the biology of the disease, to find out why not all asthma sufferers respond to treatments in the same way, and to use this information to identify, develop and test new drugs. The only problem is that we currently have to use animals to do much of this work but the animals used (mainly mice) do not spontaneously develop asthma. For this reason, they are not thought to be a good model of human asthma which may mean we miss vital information important for our research. This project aims to use methods being used to grow tissues in the laboratory (called ‘tissue engineering') to build ‘living' models of the human asthmatic lung (and healthy tissue for comparison) that can be used to understand this disease and test new drugs.

Impacts

Publications

  1. Bridge JC et al. (2015). Adapting the Electrospinning Process to Provide Three Unique Environments for a Tri-layered In Vitro Model of the Airway Wall. Journal of visualized experiments : JoVE 101:e52986. doi: 10.3791/52986
  2. Htwe SS et al. (2015). Investigating NF-κB signaling in lung fibroblasts in 2D and 3D culture systems. Respiratory Research 16:144. doi: 10.1186/s12931-015-0302-7
  3. Kaur D et al. (2015). IL-33 drives airway hyper-responsiveness through IL-13-mediated mast cell: airway smooth muscle crosstalk. Allergy 70(5):556-67. doi: 10.1111/all.12593
  4. Harrington H et al. (2014). Immunocompetent 3D model of human upper airway for disease modeling and in vitro drug evaluation. Mol Pharm. 11(7):2082-91. doi: 10.1021/mp5000295
  5. Morris GE et al. (2014). A novel electrospun biphasic scaffold provides optimal three-dimensional topography for in vitro co-culture of airway epithelial and fibroblast cells. Biofabrication 6(3):035014. doi: 10.1088/1758-5082/6/3/035014
  6. Morris GE et al. (2014). Human airway smooth muscle maintain in situ cell orientation and phenotype when cultured on aligned electrospun scaffolds. Am J Physiol Lung Cell Mol Physiol. 307(1):L38-47. doi: 10.1152/ajplung.00318.2013
  7. Rogers CM et al. (2014). A novel technique for the production of electrospun scaffolds with tailored three-dimensional micro-patterns employing additive manufacturing. Biofabrication 6(3):35003. doi: 10.1088/1758-5082/6/3/035003
  8. Harrington H et al. (2013). Self-reporting scaffolds for 3-dimensional cell culture. J Vis Exp. 7:(81):e50608. doi: 10.3791/50608
  9. Harrington H et al. (2013). Electrospun PLGA fibre sheets incorporating fluorescent nanosensors: self-reporting scaffolds for application in tissue engineering Analytical Methods 1. doi: 10.1039/C2AY25771H
  10. Clifford RL et al. (2012). Abnormal histone methylation is responsible for increased vascular endothelial growth factor 165a secretion from airway smooth muscle cells in asthma. Journal of Immunology 189(2):819-31. doi: 10.4049/jimmunol.1103641
  11. Kondrashov A et al. (2012). Inhibition of polyadenylation reduces inflammatory gene induction. RNA 18(12):2236-50. doi: 10.1261/rna.032391.112
  12. Markwick LJ et al. (2012). CCR3 induced-p42/44 MAPK activation protects against staurosporine induced-DNA fragmentation but not apoptosis in airway smooth muscle cells. Clinical and Experimental Allergy 42(7):1040-50. doi: 10.1111/j.1365-2222.2012.04019.x
  13. Patel J et al. (2012). Ciclesonide inhibits TNFα- and IL-1β-induced monocyte chemotactic protein-1 (MCP-1/CCL2) secretion from human airway smooth muscle cells. American Journal of Physiology-Lung Cellular and Molecular Physiology 302(8):L785-92. doi: 10.1152/ajplung.00257.2011