HT chemical manipulation of foetal and adult stem cells - selection transfection and scaffold identification

The cells we will study, so-called Mesenchymal stem cells from bone marrow, are very special as they have the potential to form a variety of tissue types such as cartilage, bone, muscle, tendon, ligament and fat. For this reason stem cells are currently one of the most exciting and promising areas for disease treatment and reparative medicine and in the future this will allow stem cell-based therapies to be developed to treat or cure diseases. Given the fact that we have an ageing population, the development of strategies to exploit stem cells to allow bone formation or the replacement or restoration of diseased or worn-out bone is a major clinical and socio-economic need. However crucial issues to allow this approach to be successful are the development of methods to allow the purification of stem cells to provide sufficient cells for tissue regeneration, and the development of tools to allow the cells to be controlled and converted into the specific cells desired. There is also a need to allow 3D scaffolds to be built to allow stem cell growth to form selected tissues. This programme of research offers a unique opportunity to identify select populations and population subsets, modulate differentiation and provide appropriate scaffolds for 3D skeletal reconstruction and bone formation.

The use of stem cells in the form of cell-based therapies is currently one of the most exciting and promising areas for disease treatment and reparative medicine. However, for this goal to be achieved, it is critical that platform technologies be generated to enable the isolation of stem cells, their transfection with both DNA and RNAi as well as the generation of scaffolds for stem cell growth and differentiation to form selected tissues. In order to address this issue we will harness the potential of High Throughput chemical arrays, screens and transfection strategies with mesenchymal stem cells to i) identifyof polymers, via micro-array screening, capable of enriching and supporting fetal mesenchymal stem cells and adult mesenchymal stem cell growth, ii) the development of HT stem cell RNAi an didenitfication of bio-mimetic chemical scaffolds / sequences to drive stem cell differentiation and to modulate stem cell plasticity. Finally we propose to examine ex vivo and in vivo our identified innovative scaffolds using bone formation form the mesenchymal stem cells as en exemplar. This programme of research offers a unique opportunity to harness the potential of polymer arrays and transfection chip technology to characterise the chemical fingerprint of fetal mesenchymal stem cells in comparison to adult mesenchymal stem cells as well as specific stromal lineages (adipocyte versus osteoblast). This potentially offers a novel approach to identify select populations and population subsets (whether skeletal or related stromal lineages such as adipogenic), modulate differentiation and will provide appropriate scaffolds for 3D skeletal reconstruction.