2nd of April 2015, Chichley Hall
Matt Dalby's talk revolved around ways to influence mesenchymal stem cell differentiation, and how these work at a molecular level. He started off with an investigation into the lower limit of these cells ability to recognise and respond to nanofeatures. When the nano-topographies on titania were smaller than 10-15nm (developed by the group of Bo Su), cells show a lower abundance of filopodia, but still seem interact with individual nano metric bumps with much smaller extensions - 'nanopodia'? The stem cells reaction to regular nano patterns with reduced adhesion (hexagonal packing) or retention of stemness (square array) is in contrast to the effect of nanodisorder (see talk by N Gadegaard) where the slight disorder of the NSQ50 pattern drives bone differentiation via a decided difference in focal adhesions (protein composition & size). In recent experiments it became clear that this seems to work in parts by influencing BMP signalling. The immediate environment of a stem cell the so called niche is hierarchically patterned with some nanometric aspects. Collagen type X has a hexagonal packing of about 100nm distance, similarly the sinusoid within the bone marrow, which is home to the potential stem cells such as pericytes. In collaboration with Maggie Cusack they used Nacre as a substrate for bone cells - as well as polymer copies of the surface topography with the results indicating that the stem cells can be instructed by the nano/micro features to form bone more efficiently. That stiffness could work as well is being explored together with Reijn Ulijn who developed self assembling fMoc hydrogels. These were able to drive cartilage, bone and neuronal differentiation using stiffness in alignment with earlier work. With a view to improve the way in which stem cells could be supported whilst they are differentiating metabolomics was used to investigate what components of the media the cells were using up, e.g. when differentiating towards cartilage, bone, or a neuronal phenotype.
Rules of substrate adhesion for growth and differentiation, derived using topographies, was investigated using responsive surfaces. Here adhesive sites (e.g. containing the RGD sequence) could be revealed by digestion off of fMoc using an enzyme (in preparation). When mesenchymal stem cells were grown on the fMoc protected surfaces with the hidden adhesive sequences the cells retained stemness. By digesting fMoc off, revealing the hidden adhesive peptides and allowing the cells to fully interact with these, the stem cells differentiated towards a bone-cell like phenotype.
Matt's group has investigated and developed an impressive array of techniques: topography (various), materials, stiffness, switchable surfaces, nanokicking, metabolite support that could be exploited to drive mesenchymal stem cell differentiation in a variety of settings.
This talk was part of a workshop on "Cell Mechanobiology" organised by Rene de Borst, which took place April 1st and 2nd 2015, with support by the Royal Society at Chicheley Hall. for the programme details see: http://bio-mat-sketches-mor.blogspot.co.uk/2015/04/cell-mechanobiology-workshop-1st-2nd.html