NANO-OPTICAL-MECHANICAL MANIPULATION OF STEM CELLS IN PHYSIOLOGICAL FLOWS: DESIGN PRINCIPLES FOR DELIVERING STEM CELL THERAPY

New therapies in stem cell treatments will require new strategies for delivering the cells to sites of injury or regenerating tissue. Methods of delivery include delivering the cells through the vascular system to tissues through the capillary bed and direct injection to the site of repair. Fluid mechanical stimulation to the stem cell during such delivery processes is critical to the cell integrity and viability. Indeed the role of shear stress in influencing a variety of cell types has been increasingly documented. In our proposed research, we will apply a new optical, mechanical tool for manipulating stem cells in microfabricated channels and study how the cells respond to such fluid mechanical stimuli. In particular, we will carry out a range of feasibility studies based on quantitative biochemical analyses of these cells after exposure to various flow conditions. We aim to bring together biologists, engineers, physicists and mathematicians in Keele and from other institutes to explore new strategies of stem cell delivery via circulation or injection. In the long term, these new delivery approaches will be useful for the advancement of cell therapy to various diseases, such as cancer and cardiovascular disorders.

A growing body of research is studying the control and maintenance of stem cell phenotype for application in a broad range of clinical therapies. In many of these examples, cells are delivered in vivo either through injection directly to the damaged tissue or relying on delivery through the vascular system. In the majority of these cases, little is known about the ability of the cells to maintain phenotype through this process, which can often involve subjecting cells to physiological flows. In this study, we set out to investigate whether these cells can be influenced by vascular delivery. In particular, we will examine whether they can withstand the high levels of stress which may be part of cell delivery, whether the level of differentiation is critical to successful delivery, and whether subjecting these cells to shear and mechanical perturbation results in an altered phenotype. Examination of these parameters is only now possible as a result of our developments in nano-optical-mechanical manipulation underpinned by advanced cell biology, instrument design, micro-fabrication, theoretical mechanics and computer simulation. This knowledge is essential for the advancement of stem cell delivery strategies.