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Prof Phil Stephens 


Ongoing Research Projects

Probing the mechanical control of stem cell fate through the development of novel, non-invasive imaging technologies (funded by the EPSRC)

The Engineering and Physical Sciences Research Council has jointly awarded Cardiff University and Swansea University £1.5M as part of their recent Novel Technologies for Stem Cell Sciencecall.

This is a cross School and cross University project led by Professor Phil Stephens (Dentistry) involving colleagues from the Schools of Biosciences (Dr Paola Borri, Dr Susan Hunter, Dr Stephen Paisey), Chemistry (Dr Eric Tippmann), Dentistry (Dr Alastair Sloan), Medicine (Dr Rachel Errington), Physics (Dr Wolfgang Langbein), the ESRC Centre for the Economic and Social Aspects of Genomics  (Dr Neil Stephens), the Cardiff Institute for Tissue Engineering and Repair and from the School of Engineering at Swansea University (Dr Karl Hawkins, Dr Chris Wright, Professor Rhodri Williams).

Whilst in our increasing ageing population stem cell science and technology holds a great deal of promise within the context of tissue repair and regeneration, moving this technology to the clinics has been relatively slow due to a number of distinct ‘barriers’. For example, whilst we know a lot about the function and response of stem cells in the laboratory, we know very little about their behaviour in tissues within individuals.  A further major barrier has been the inability to accurately track cell lineages and to distinguish them from other cell types within the tissue (i.e. when one cell divides to become two cells are they the same or different?  Is this effect the same or different each time the cell divides? Where do they go?).  The project will address these issues by bringing together researchers across different scientific disciplines in the physical and life sciences to develop novel technologies for stem cell science.  We will develop new ways of non-destructively labelling stem cells by manipulating molecules within the cells so we can follow both their position and their eventual fate (i.e. what do these stem cells turn into?).  In order to image the cells we will develop new microscopic techniques that allow us to view these cells in a non-invasive, non-harmful way (unlike current approaches) and we will utilise technologies that will eventually enable us to image these cells deep within patient tissues.  Being able to follow these stem cells will allow us to examine the mechanical influence of their surrounding tissue environments.  Armed with such knowledge we will mechanically manipulate the surrounding environment to direct stem cells into our tissue of choice in order to deliver custom designed tissues on demand (either within the laboratory or eventually within a patient).  Overall, our ultimate aim is to develop new tools to allow us to investigate and control stem cell biology in order to realise the true clinical potential of these cells.

 

Oral mucosal progenitor cells, preferential wound healing outcome and immunomodulation (funded by the WORD)

Over the past decade we have reported that patient matched oral mucosal and skin fibroblasts have distinct phenotypic and genotypic differences which result in the preferential healing response seen within the oral mucosa These findings support the idea that a progenitor cell (PC) population may be resident specifically within the oral mucosal lamina propria (OMLP) and it is this cell population that may contribute to the preferential healing response seen on wounding of this tissue.  Importantly, isolation of a PC population from the OMLP would offer distinct advantages for therapeutic applications, providing a site of biopsy that is easily accessible and minimally invasive, with rapid healing and no/minimal resultant scar formation for the patient.

We have now demonstrated the existence of this novel, neural crest-derived PC population resident within the lamina propria of the oral mucosa (Davies et al., 2010 in press; UK patent applications GB810841.7, GB0811865.5, GB0820012.3 & International patent application GB09/001443).  Single cell clones isolated from these tissues have been rapidly expanded in vitro, are neural crest-derived and are multipotent (mesenchymal, neuronal and glial lineages).  We are now investigating their immunomodulatory capacities.

 

The development of in vitro alternatives to animal wound model systems (funded by the NC3Rs)

Chronic wounds, such as diabetic foot ulcers, result in impaired wound healing in 3-5% of the population over the age of 65. However, despite the increasing financial burden of these diabetic wounds there is, at present, no suitable diabetic chronic wound animal model. Therefore, in the light of the concerns and limitations of animal models and human testing, this NC3Rs Grant application will develop a stable, reproducible, in vitro diabetic wound model system. This will permit rapid, low cost testing of materials, reagents and drugs in order to reduce unnecessary animal experimentation. We have already demonstrated that venous leg ulcer derived fibroblasts (CWF) and diabetic foot ulcer fibroblasts (DF) are phenotypically distinct from patient-matched normal fibroblasts (NF). We have also immortalised both the NF and DF (by retroviral insertion of the human telomerase) to create stable, disease-specific cell lines and within these cells have identified disease specific marker genes by microarray analysis. The aim of this NC3Rs Grant application will be to extend these initial studies/findings and, using a virus integration approach, stably transduce our immortalised disease cells with fluorescent disease marker gene reporter constructs. This will give us a robust, cell-based reporter system, enabling automated testing and pre-screening of reagents which may ameliorate the diabetic wound disease state. It is anticipated that at the end of the funding we will be close to commercialising the bioassay and developing a high-throughput screening system, which will reduce the amount of unnecessary animal studies undertaken with respect to wound product/materials testing. We believe that the development of such an in vitro diabetic wound model will represent an important and unique resource for wound healing researchers Worldwide.

 

Current Funding

EPSRC (2010-2013; multi-centre grant)
Wales Office of Research and Development for Health and Social Care (2010-2011)
NC3Rs (2009-2011)              

Previous funding:

Wellcome Trust Value in People award (2007-2008)
The Osteology Foundation (2007-2008)
Research into Ageing (2006-2009)
EPSRC (2006-2009; multi-centre grant)
NC3Rs (2006-2009)
Wales Office of Research and Development for Health and Social Care (2006-2007)
The Dr Hadwen trust (2004-2007)
Diabetes UK (2004-2007)
NC3Rs/LASA Small Award Scheme (2007)
Royal College of Surgeons (Edin) (2004-2005)
Johnson & Johnson (2003-2004)
Royal College of Surgeons (Edin) (2003-2004)
British Association of Oral and Maxillofacial Surgeons (2003-2004)
FMC, Norway (2002-2004)
Johnson & Johnson (2001-2003)
Johnson & Johnson (2001-2003)
Astratech, Sweden (2001-2002)
Wales Office of Research and Development for Health and Social Care (2001-2002)
Wales Office of Research and Development for Health and Social Care (2001-2002)
Research Into Ageing - Dyne Steel Wound Healing Research Fellowship (2000-2002)
Research Into Ageing (1999-2000)
Oral and Dental Research Trust, The Colgate Research Award (1999)
National Institutes of Health, USA (1998-2003)
Veterans Affairs Medical Center, USA (1998-2001)
Beiersdorf AG, Germany (1996-1998)
Oral and Dental Research Trust, The Colgate Research Award (1996)