Accelerating biomarker discovery on the surface of unique stem cell lines and validation of the functionality of lead candidates

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.