Stem Cell Research
Here we are combining more conventional methods for guiding stem cell differentiation, such as biochemical stimuli and gene manipulation with less well investigated biophysical approaches. Specific projects include investigating the effects of nano- and micro-topography and also scaffold porosity and viscosity in both 2-D and 3-D environments on, for example, the osteochondral differentiation of embryonic stem cells with polylactide scaffolds, differentiation of corneal stem cells within hydrogels and maintenance of gut stem cells on porous polymer membranes co-cultured with myofibroblasts.
The biology of stem cells is strongly influenced by micro-environmental / niche stimuli and we have a number of projects to simulate such environments. For example, in collaboration with other members of the school of Pharmacy (Drs M. Alexander, S.Allen and P. Williams) micro-mechanical forces are being investigated to stimulate and potentially to also monitor growth and differentiation of both embryonic and bone marrow stem cells. In collaboration with Profs M. Padgett and J. Cooper (University of Glasgow) we are using holographic optical tweezers to capture and position stem cells into defined 2-D and 3-D positions to further investigate the effects of cell-cell interactions and localized signalling on stem cell biology. We also have a large multi-project collaboration with Mathematical Sciences at Nottingham (Profs J. King, O. Jensen, H. Byrne and Drs S. Waters and M. Owen) and are combining experimental data with mathematical modelling approaches to understand and to develop better experimental approaches to investigate for example, cell differentiation within embryoid bodies, formation of specific tissue structures, such as the intestinal crypt and induction of angiogenesis within porous scaffolds.
Another important aspect of stem cell research is to understand potential similarities and differences between different sources of stem cells. We are therefore involved in a large multi-centre/-country European Union Framework VI project to investigate and compare the osteogenic differentiation of human cord blood, bone marrow and embryonic stem cells (OSTEOCORD; www.bonefromblood.org).
Human embryonic stem cells (a) and induction of osteogenic differentiation via embryoid bodies (b) to form mineralizing bone-like tissue in vitro (c) and within a polymer scaffold in vivo (d). Stains: Alizarin red (c) and osteocalcin (d). Scale bar = 100 µm