| EPSRC Reference: |
EP/N510105/1 |
| Title: |
Development of a novel 3D microfluidic assay platform for the assessment of human stem-cell derived epithelial function. |
| Principal Investigator: |
Morgan, Professor H |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Electronics and Computer Science |
| Organisation: |
University of Southampton |
| Scheme: |
Technology Programme |
| Starts: |
29 March 2016 |
Ends: |
28 March 2018 |
Value (£): |
149,894
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| EPSRC Research Topic Classifications: |
| Med.Instrument.Device& Equip. |
Tissue engineering |
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| EPSRC Industrial Sector Classifications: |
| Healthcare |
Pharmaceuticals and Biotechnology |
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| Panel History: |
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Summary on Grant Application Form |
Every day we inhale more than 10,000 litres of air into our lungs, so it is not surprising that we have developed effective defence mechanisms against many of the invisible components (bacteria, viruses, dust, pollutants etc) contained in the air we breathe. In particular, so-called 'epithelial' cells that line the surface of our airways are very important as they form a barrier that protects us against these agents and help keep our lungs healthy. However in people who have chronic lung diseases such as asthma or bronchitis these cells do not function properly and as a result the protective barrier is compromised and the lungs become more sensitive to environmental triggers such as allergens or viruses. If we could understand more about what goes wrong with the epithelial barrier, it would be possible to develop new and more effective drugs for respiratory diseases. For many years, human diseases have been studied using 'animal models' that demonstrate features of the disease. While these models have given valuable information about mechanisms of cell regulation, direct transfer of the results into therapies for human disease has been problematic. Therefore, there has been a move towards studying cells derived from human volunteers using models that are grown in the laboratory under conditions that aim to mimic aspects of their function in the lung. These models have been widely used but they are relatively simple and do not have all the components present in the human body such as blood flow. They also require an endless source of human cells which are difficult to obtain and can show considerable donor variability.
To solve this problem we will develop a lab-on-a-chip device that can be made from inexpensive plastics and integrates several laboratory functions on a single chip of less than a square centimetre in size. This user-friendly miniaturised device will be used to grow lung cells that can be derived in almost limitless supply from adult human stem cells. The cells will be grown in the chip where they make an epithelial barrier and provide a model for airway tissue with air on one side and liquid on the other. It also provides constant flow around the tissue and is designed to provide nutrients and remove waste products as occurs in the body; it also enables small samples of the liquid surrounding the tissue to be collected at different time points to monitor the behaviour of the epithelial cells. We will also monitor the electrical properties of the epithelial barrier formed by the lung tissue in the chip so that the effect of environmental triggers can be followed. In this way we will create a 'Smart biochip' that provides a sustainable and accessible model of the airway epithelial barrier which can be challenged with environmental triggers (such as house dust, pollen or viruses) and used to investigate the effects of potential new drug therapies in comparison with established anti-inflammatory therapies such as steroids.
The objectives of the project are:
-design, fabricate and test different versions of chip to give the optimum tissue structure and function that most closely resembles the lung tissue.
-develop the supporting hardware and software to control fluid flow, sample collection and measure the barrier.
-develop simplified methods to make lung cells from adult human stem cells.
-use the Smart Biochip to test drugs provided by pharmaceutical collaborators.
This new technology has the potential to more accurately predict responses of lung tissue to drug therapies, shorten the length of time of drug development from drug discovery to trials in humans and identify new drug targets. This system will enable new experiments which will lead to an improved understanding of diseases of the airways. The platform will also provide a simple, fast way to perform toxicology and pharmacology screens of new and existing drugs and compounds such as aerosols that we inhale or exposed to in our daily life
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.soton.ac.uk |