Development nanoparticle-based techniques to monitor differentiating neural stem cells after transplantation

There is much excitement about the possibility of using stem cells to replace diseased, damaged or even underdeveloped tissues. However, before such therapies can be devised, we need to be able to follow what happens when stem cells (or the cells they develop into) are transplanted into the body. Our project intends to make use of another recent scientific development, using nanotechnology to be able to follow the development of stem cells. To do this, we will modify the chemistry of metallic nanoparticles (which have diameters of less than ten thousandth of a millimeter) so that they are taken up by stem cells. By observing the localisation of these particles we can in turn locate the stem cells which took them up, even though those stem cells may have already developed into different types of cell.

Although there is currently increasing research using nanoparticle-based imaging to track stem cells and their derivatives, little work has been done to develop these techniques so that the nanoparticles are directed to specific sub-cellular locations. Such specificity is necessary for example, if developing axons are to be followed after transplantation of neural stem cells or their derivatives. This proposal therefore seeks to optimize nanoparticle-based cell tracking techniques to achieve subcellular localisation, demonstrated by comparison with existing lentiviral-based fluorescent protein reporter assays. To do this, we will build on two previously unconnected fields of research in Liverpool (a) the development of physico-chemical methods for the construction and modification of a variety of nanoparticles (including Quantum-dots and gold nanoparticles), which will be used to produce nanoparticles modified with a variety of cell specific targeting ligands and (b) the development of an in vitro assay system that faithfully reproduces the migration and differentiation of enteric nervous system stem cells to innervate the gut, which can be used to assess the ability of the nanoparticles to follow cell development of developing neurones and their axons after transplantation. Production of such nanoparticle reagents will aid to future clinical development and is also likely to be of relevance to a variety of next-generation nano medical applications.