Bôn Gelloedd, Atgyweirio Clwyfau ac Adfywio
Our research aims to understand the mechanisms underlying the repair and regeneration of oral, dermal and neural tissues during health and disease.
By understanding these mechanisms, our objectives are to develop stem cell, pharmaceutical, biomaterial, bioelectrical and other therapeutic strategies to promote wound repair in these and other tissues throughout the body.
Despite significant medical advancements in recent years, clinical conditions associated with impaired or dysfunctional wound healing remain major healthcare challenges, especially with the rising incidence of these conditions in ever-increasing ageing populations worldwide and the acknowledged inadequacies in current wound treatment options.
Research within Stem Cells, Wound Repair & Regeneration aims to enhance our understanding of the cellular and molecular mechanisms regulating the repair and regeneration of oral, dermal and neural tissues during health and disease. We are particularly focussed on the basic cellular biology of oral- and neural-tissue derived, mesenchymal stromal cells, neural crest progenitor cells and induced pluripotent stem cells. As part of achieving impact on patient health and well-being, we are also focussed on the delivery and translational development of exogenous stem cells as clinical therapies for the treatment of acute and chronic diseases.
Other key areas of research utilise our knowledge of the mechanisms underpinning normal and aberrant wound h\ealing processes to develop pharmaceutical, biomaterial, bioelectrical and other therapeutic approaches, which restore or enhance molecular signalling events and repair/regeneration responses in endogenous and exogenously-applied cells, leading to more successful wound healing outcomes.
Through these research initiatives, our objectives are to facilitate the advancement of novel and more effective treatments, which overcome the inadequacies surrounding existing wound repair therapies and drive improvements in the patients’ quality of life.
Contrasting wound healing mechanisms in oral mucosa & skin tissues
Wounds in the mouth heal extremely well compared to normal skin wounds, as oral mucosal wounds demonstrate minimal inflammation, more rapid healing and reduced scarring. We have investigated the differences between the fibroblasts derived from the oral mucosa and skin, identifying that the preferential healing and reduced scarring properties of the oral mucosa relate to an ‘enhanced’ wound healing fibroblast phenotype.
We are interested in understanding the mechanisms responsible for these preferential healing responses in oral mucosal fibroblasts, to identify novel pathways to be targeted by newly-developed therapies to help repair/regenerate damaged or diseased tissues.
Oral mucosal progenitor cells for tissue repair
The preferential healing capabilities of the oral mucosa may also suggest that oral mucosal cells are more foetal or stem cell-like in nature. Our recent work has identified such stem cell−like cells within the oral mucosa, which are capable of differentiating down multiple lineages.
In addition, these cells have been demonstrated to possess potent anti-bacterial and immuno-suppressive properties. Hence, we are investigating the potential of these cells to help down-regulate the immune system in patients during transplantation, auto-immune diseases or those combating chronic infections.
Mechanisms underlying impaired healing in chronic skin wounds
Non-healing, chronic skin wounds (such as venous leg ulcers, diabetic foot ulcers) are an important source of morbidity in ageing societies and a significant financial burden to healthcare providers. These wounds are characterised by bacterial contamination/infection, prolonged inflammation, defective matrix turnover; and delayed wound re-epithelialisation and closure.
Our research is focussed on elucidating the mechanisms responsible for impaired cellular wound healing responses in chronic wounds, with the aim to utilise this information to develop novel therapies to restore healing potential in these wounds.
Mechanisms underlying dysfunctional spinal cord repair
Spinal cord injury (SCI) frequently provokes serious derimental outcomes, as neuronal regeneration is limited in the central nervous system. Consequently, SCI is one of the leading causes for long-term disability in the Western world, as current treatments have limited efficacy and significant functional improvements remain difficult to achieve.
Our research is currently evaluating the role of the immuno-inflammatory responses in the pathogenesis of SCI, in addition to assessing the potential of biomaterial, microfluidics, growth factor and stem/progenitor cell (e.g. neural, oligodendrocyte and dental pulp) strategies for the replacement of lost neuronal cells, promotion of repair and functional plasticity.
Electrical signal regulation of stem cell behaviour, wound healing & nerve regeneration
In contrast to more conventional therapeutic approaches to enhancing repair, there has also been a long-standing interest in the concept of electrically stimulating wound healing. The application of exogenous electrical fields at physiologically relevant levels can enhance repair processes, via the stimulation of signals responsible for cellular migration, proliferation and differentiation, in tissues including skin and the central nervous system.
We are interested in identifying the optimal electrical stimulation conditions necessary to promote enhanced neural and dermal wound healing; and the underlying mechanisms by which these responses are induced.
Pharmaceutical therapies for the enhancement of wound healing
Existing therapies aimed at treating impaired healing wounds or excessive scarring situations are established to offer limited benefit to healing outcomes or scar prevention. Therefore, we are currently working with academic and industrial collaborators to evaluate the potential of a number of novel pharmaceuticals, in terms of their abilities to restore or enhance normal healing functions and/or reduced scarring in these patients.
- Jiang, W. et al. 2019. Wnt-GSK3ß/ß-catenin regulates the differentiation of dental pulp stem cells into bladder smooth muscle cells. Stem Cells International 2019 8907570. (10.1155/2019/8907570)
- Melling, G. et al. 2018. Liposomal delivery of demineralised dentine matrix for dental tissue regeneration. Journal of Tissue Engineering 24 (13-14), pp.1057-1065. (10.1089/ten.TEA.2017.0419)
- Dally, J. et al. 2017. Hepatocyte growth factor mediates enhanced wound healing responses and resistance to transforming growth factor-β1-driven myofibroblast differentiation in oral mucosal fibroblasts. International Journal of Molecular Sciences 18 1843. (10.3390/ijms18091843)
- Avery, S. et al. 2017. Analysing the bioactive makeup of demineralised dentine matrix on bone marrow mesenchymal stem cells for enhanced bone repair. European Cells and Materials 34 , pp.1-14. (10.22203/eCM.v034a01)
- Alraies, A. et al. 2017. Variation in human dental pulp stem cell ageing profiles reflect contrasting proliferative and regenerative capabilities. BMC Cell Biology 18 12. (10.1186/s12860-017-0128-x)
- Howard-Jones, R. A. et al. 2016. Integration-free reprogramming of lamina propria progenitor cells. Journal of Dental Research 95 (8), pp.882-888. (10.1177/0022034516637579)
- Young, F. et al. 2016. Clonal heterogeneity in the neuronal and glial differentiation of dental pulp stem/progenitor cells. Stem Cells International , pp.1-10. 1290561. (10.1155/2016/1290561)
Recent grant awards
- Engineering and Physical Sciences Research Council (EPSRC) (2010-14). Probing the mechanical control of stem cell fate through the development of novel, non-invasive imaging technologies. £1,545,307
- European Research Council (ERC) (2010-15). Repair spinal cord injury by controlling migration of neural stem cells. £1,760,000
- Medical Research Council (MRC) (2011-14). Oral mucosal lamina propria progenitor cells as a novel and preferential source for treatment of Graft Versus Host Disease. £387,948
- Malaysian Government, Ministry of Higher Education (2011-14). Growth factor responsiveness and bone repair mediated by bone marrow-derived stem cell during type II diabetes. £66,000
- Qbiotics Ltd. (2012-2015). Stimulatory effects of epoxy-tiglianes on dermal fibroblast and keratinocyte wound healing responses. £119,806
- Medical Research Council (MRC) (2014-15). Progenitor cell-based interventive therapies for improved tissue transplantation. £50,000
- Sêr Cymru (Life Sciences Research Network Wales) & QBiotics Ltd. (2014-2017). Pharmaceutical evaluation of novel tigliane compounds as modulators of dermal fibroblast-myofibroblast differentiation, scar tissue resolution and fibrosis; and elucidation of their underlying mechanisms of action. £105,190
- Iraqi Government, Ministry for Higher Education and Scientific Research (2014-17). Altered bone cell biology associated with type 2 diabetes mellitus: Consequences for periodontal disease. £90,000
- National Institute for Social Care and Health Research (NISCHR) (2014-17). Role of microRNA-7 in impaired TGF-b1-driven differentiation in chronic wound fibroblasts. £66,000
- Wellcome Trust (2015). Stem cell tracking and controllable cell death via Positron Emission Tomography superparamagnetic iron oxide nanoparticles. £16,833
- Wellcome Trust (2015-16). Equipment award, Cell-IQ: time resolved cell tracking. £100,000
- Australian National Health and Medical Research Council (NHMRC) (2015-18). Development of a novel drug for chronic and infected wounds. AU$467,975
- School of Dentistry, Cardiff University & ReNeuron plc (2015-18). Progenitor cell-based interventions for tissue repair. £92,566
- Saudi Arabian Government, Ministry of Defence (2015-18). Role of oxidative stress responses in clonal variations in dental pulp progenitor cell ageing and regenerative potential. £87,000
- Cardiff University Biobank (2015-). £1,500,000
External academic collaborators
- Professor Peter Parsons & Dr Glen Boyle, QIMR Berghofer Medical Research Institute, Australia.
- Dr Steven Ogbourne & Dr Fraser Russell, University of the Sunshine Coast, Australia.
- Dr Mark Bass & Dr Simon Whawell, University of Sheffield, UK.
- Mr Elijah Ablorsu, Cardiff and Vale University Health Board, UK.
External industrial collaborators
- Dr Paul Reddell, QBiotics Ltd., Australia.
- Dr Randolp Corteling, ReNeuron plc, UK.
- 2015: CITER Oral Presentation Prize (Lorena Hidalgo San Jose).
- 2014: ETRS Poster Prize (Rachael Moses).
- 2014: TCES Poster Prize (Rachel Howard-Jones).
- 2014: CITER Oral Presentation Prize (Emma Board-Davies).
- 2013: TCES Oral Presentation Prize (Adam Glen).
- 2012: BSODR Senior Colgate Prize (Rachel Howard-Jones).
- 2012: BSODR Unilever Poster Prize (Amr Alraies).
- European (EP1245239) and US (US2003040690) patents, relating to the antioxidant properties of wound dressing-based biomaterials.
- European (EP1889069), UK (GB2426335), US (US2009299161) and Worldwide (WO2006123091) patents, relating to the use of total antioxidant capacity as a prognostic/diagnostic biomarker of of chronic wound infection and healing.
- UK (GB2447865), US (US2010166694, US2012010099) and Worldwide (WO2008119974) patents, relating to the quantification of various cytokines and growth factors as prognostic/diagnostic biomarkers of diabetic foot ulcer wound infection and healing.
- Australian (AU2006317523, AU20100213362), Brazilian (BRPI0618926), Canadian (CA2629899, CA2752389), Chinese (CN101360506, CN102316866), European (EP1965818, EP2395993), Japanese (JP2009517345, JP2012517450), Korean (KR20080077625), New Zealand (NZ568168, NZ594184), Russian (RU2011137530), US (US2009215884, US2012041064); and Worldwide (WO2007059584, WO2010091472) patents, relating to the application of ingenol mebutate and related compounds in the promotion of dermal wound healing and reduced scarring.
- Australian (AU2009259053), Chinese (CN200980122121), European (E09761964), Japanaese (JP501125275); and US (US12/997,363) patents, relating to the isolation and use of a novel progenitor cell population from the oral mucosal lamina propria for clinical applications.
- Worldwide (WO2014169356) patent, relating to the application of epoxy-tigliane compounds in the promotion of dermal wound healing and reduced scarring.
Cyfarwyddwr Cyswllt Ymgysylltu a Menter, Professor in Oral Biochemistry, Director of Postgraduate Research Studies
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