The use of stem cells in the form of cell-based therapies is currently one of the most exciting and promising areas for normo- and patho-physiology and disease treatment with an emphasis on reparative and regenerative biology. However, for this goal to be achieved, it is critical that the fundamental biological processes and characterisation are thoroughly met in a timely and state-of-the-art approach. The use and development of exisiting platform technologies needs to be improved to enable the isolation of unique mesenchymal stem cells. The isolation and purification of specific populations of cells will aid in our understanding of their function in regards to bone biology as well as attempts to modulate their activity. For example, transfection with DNA and RNAi as well as the generation of scaffolds for stem cell growth and differentiation to form selected biological tissues can only be realised with pure cell populations. A key issue however is the ability to identify and provide sufficient stem/progenitor populations for tissue regeneration. We propose that a paradigm shift in current research technology and application is required if we are to meet and improve our understanding of stem cell fate, differentiation, expansion and potentiality and thus the goal of stem cell utility for future therapeutic application. We will use a novel strategy employing an existing protein discovery platform to sort rare cell populations in order to identify protein markers that are not found by conventional approaches. Typical proteomics, RNA profiling, monoclonal antibodies and genomic profiling approaches have struggled in cell surface marker discovery due to the high 'noise' signal from the common cell populations which obscure those from the rare ones in unseparated cell populations. This CASE application is between Ovasort Ltd, an SME and the University of Southampton. This application is unique as it builds on exisiting research interactions between the applicants in novel protein discovery at the cell surface in a variety of cell types. This application blends technological development for discovery enhancement and biological assessment of newly identified cell surface proteins that may have a differential and functional role in identifying mesenchymal stem cells. In order to achieve this we will work with our academic partner, Professor Richard Oreffo and aim to: 1. functionally characterise cell surface proteins - do they have a role in or / and act as a marker for differentiation? 2. undertake translational biomedical science - validation of marker utility using clinically obtained and approved human tissues; 3. perform state of the art training and development of a PhD student in academia and industry.

Regenerative medicine aims to develop biomaterial and cell-based therapies that restore function to damaged tissues and organs. It is a cornerstone of contemporary and future medicine that needs a multidisciplinary approach. There is a world-wide shortage in scientists with such skillsets, which was highlighted in 2012 by the Research Councils UK in their 'A Strategy for UK Regenerative Medicine" which promotes 'training programmes to build capacity and provide the skills-base needed for the field to flourish'. The major clinical need for regenerative medicine was highlighted by the Science and Technology Committee (House of Lords; July 2013), who identified that 'The UK has the chance to be a leader in [regenerative medicine] and this opportunity must not be missed', and that 'there is likely to be a £44-54bn NHS funding gap by 2022 and that management of chronic disease accounts for around 75% of all UK health costs'. Vascular diseases are the leading cause of death and disability worldwide, musculoskeletal diseases have a huge burden in pain and disability, diabetes may be the 7th leading cause of death by 2030, and peripheral nerve injuries impair mobility after traumatic injuries. There is a pressing need for commercial input into regenerative medicine. Whilst the next generation of therapies, such as stem cells and biomaterials, will be underpinned by cutting-edge biology and bioengineering, strong industrial-academic partnerships are essential for developing and commercialising these advances for clinical benefit. We have established strong industrial partnerships which will both enhance the CDT training experience and provide major added value to our industrial partners. Regenerative medicine is a top priority for the University of Manchester (UoM) which has excellence in interdisciplinary graduate training and a critical mass of internationally renowned researchers, including newly appointed world-leaders. Our regenerative medicine encompasses physical, chemical, biological and medical sciences; we focus on tissue regeneration and inflammation, engineering and fabrication of biomaterials, and in vivo imaging and clinical translation, all on our integrated biomedical campus. We propose a timely Centre for Doctoral Training in Regenerative Medicine in Manchester that draws on our exceptional multidisciplinary depth and breadth, and directly addresses the skills shortage in non-clinical and clinical RM scientists. Our expertise integrates tissue regeneration & repair, the design & engineering of biomaterials, and the clinical translation of both biological and synthetic constructs. Our centres of excellence and internationally-leading supervisors across this multidisciplinary spectrum (details in Case for Support and UoM Letter of Support) highlight the strength of our scientific training environment. Defining CDT features will be: integrated cohort-based multidisciplinary training; skills training in engineering, biomedical sciences and pre-clinical translation; imaging in national Large Facilities; medical problem-solving nature of clinically co-supervised PhD projects, including in vivo training; comprehensive instruction in transferable skills and commercialisation; outward-facing ethos with placements with UK Regenerative Medicine Platform hub partners (UoM is partner on all three funded hubs), industrial partners, and international exchanges with world-class similarly-orientated doctoral schools; presentations in seminars and conferences. In this way, we will deliver a cadre of multidisciplinary scientists to meet the needs of academia and industry, and ensure the UK's continuing international leadership in RM. Ultimately, through training this cadre of doctoral scientists in regenerative medicine, we will be able to improve wound healing, repair injured nerves, blood vessels, tendon and ligaments, treat joint disease and restore function to organs damaged by disease.