Interactions of mesenchymal stem cells with synthetic surfaces

As part of the BBSRC's priority to enhance the Cell Supply Chain (Engineering and Biological Systems Committee) we wish to investigate methods of improving the interactions between biomaterials and mesenchymal stem cells. The use of mesenchymal stem cells in orthopaedic applications is established in the use of bone marrow aspirate and more recently in the use of isolated, purified and expanded homogenous cell populations. Within the body, the local niche within which mesenchymal stem cells reside is important in maintaining the cell phenotype. In response to injury the stem cell niche changes and the cells are stimulated to play a central role in bone repair. Future success of medical applications of mesenchymal stem cells will be dependent on the delivery of cells into the body in a manor that recreates a suitable niche to maintain cell viability and to boost regeneration. To underpin this work we wish to use BBSRC funding to explore how the surfaces of injectable cell delivery systems can be modified to stimulate appropriate cell adhesion and subsequent activities. Cell delivery systems are a new class of biomaterials that carry stem cells into the body and then create a 3D porous environment around the cell population. The biomaterial is normally highly porous and therefore presents a massive surface area to the cell population. The available surface can be engineered to present whole proteins and peptides that bind to specific integrin receptors. Other growth factor mediated effects on cells can also be stimlated with such a surface engineering approach. The student supervisor will be Professor Kevin Shakesheff, School of Pharmacy, The University of Nottingham. Under this project the student will collaborate with Ms Brigitte Scammell (Orthopaedic Surgeon and Academic) to isolated and characterise human mesenchymal stem cell populations. Following a careful literature review the student will surface engineer polymer surfaces with peptides that bind to the cells (this builds on work by Professor Shakesheff in collaboration with the University of Southampton, BONE 29 (6): 523-531 DEC 2001). The ability to augment osteoconductive behaviour (with additional ceramic components added to the biomaterial) will be used as in vitro quantification methodology. The student will work with Ms Scammell to develop animal models to quantify the effect of surface engineering on angiogenesis and bone repair.