Development of a novel 3D microfluidic assay platform for the assessment of human stem-cell derived epithelial function.

Lead Research Organisation: University of Southampton
Department Name: Electronics and Computer Science

Abstract

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.

Planned Impact

Another major impact from this project will be a significant reduction in the use of animals in respiratory research.
Importantly, many animal models of respiratory diseases may involve procedures of moderate severity and have end points
where animals are sacrificed for collection of tissues. Although national and international statistics do not provide sufficient
details about the number of animals used to study respiratory diseases, in 2012 over 87,000 animals were used in
respiratory research in Britain, two- thirds of them in mice. By developing an alternative human-based in vitro model for
investigating respiratory diseases we believe that many animal models can be replaced in the future. We acknowledge that
in vivo animal models are not completely substitutable by in vitro models. By using a multi-disciplinary approach, the
proposed project will be a valuable alternative to animal studies of respiratory diseases.
As an academic institution, the University of Southampton aims to inspire and equip future generations of biomedical
scientists and clinicians to meet the challenges of a changing world. Our project addresses this aim - not only will we equip
the postdoctoral researcher with cross disciplinary skills in physical and life sciences, but we will also expose them to
working closely with large and small commercial partners. In addition, training will be given to researchers in SAL Scientific,
enhancing the skills of this workforce in areas of respiratory epithelial cell biology. These benefits will be achieved within
the timeframe of the project.

Publications

10 25 50
 
Description This project is a partnership with GSK and SALScientific. It aims to recapitulate the human airways outside the body in a small microfuidic chip to enable testing and development of new drugs. We have discovered ways to grow the cells in the chips and ways to monitor in real time the biophysical properties of the model airways.
Exploitation Route The "lung on a chip" is being used by pharmaceutical company such as GSK to develop new drugs, to personalise therapy and to screen for toxic compounds. It could also be used to understand the physiology of the human airways and to model the interaction of viruses with cells of the lung.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The research from this project has increased the business capability of our partner SME SALScientific. The company has made significant progress in the establishment of epithelilal stem cell lines. It will also enable GSK to improve drug development and reduce the attrition in failure at stage III clinical trial.
First Year Of Impact 2018
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Lung on Chip 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Development of new technologies for ex-vivo tissue engineered constructs for drug screening and personalized medicine
Collaborator Contribution Provision of new stem cell technologies
Impact This is a multidisciplinary project that is developing a new approach to growing artificial human airways outside the body. This will be made using either the patient's own cells or stem cells grown in the lab. The proof of principle of this technology has been establshed and we are now moving towards developing a device that can be used by industry.
Start Year 2016
 
Description Lung on Chip 
Organisation SAL Scientific
Country United Kingdom 
Sector Private 
PI Contribution Development of new technologies for ex-vivo tissue engineered constructs for drug screening and personalized medicine
Collaborator Contribution Provision of new stem cell technologies
Impact This is a multidisciplinary project that is developing a new approach to growing artificial human airways outside the body. This will be made using either the patient's own cells or stem cells grown in the lab. The proof of principle of this technology has been establshed and we are now moving towards developing a device that can be used by industry.
Start Year 2016
 
Title A method of electrically measuring the electrical properties of individual particles flowing in a liquid 
Description This patent 
IP Reference US20160041080 
Protection Patent application published
Year Protection Granted 2019
Licensed Commercial In Confidence
Impact No non-economic impacts as yet.