Objective Magnetic Resonance contrast agents for non-invasive monitoring of the differentiation of embryonic stem cells into brain cells will be developed and tested in an animal model. These contrast agents (CA) will revolutionise our understanding of cellular differentiation processes by visualising "cells at work" in vivo with high spatial and temporal resolution. In contrast to other molecular imaging techniques, magnetic resonance imaging (MRI) is not limited to invasive ex vivo studies or the outermost layer o f biological tissue like optical techniques.Chelated Gadolinium-based MRI CAs will be designed and synthesised so that enzymes specifically expressed after the differentiation of stem cells will generate a contrast by activating the `silent¿ CA through chemical modification. No transfection of cells is required for visualisation. In order to address a variety of differentiation processes, a number of different CAs will be generated, which focus on enzymes responsible for the synthesis of neurotransmitters, but also compounds that distinguish between neuronal and astrocyte metabolism. Contrast agents will be synthesised and provided by the laboratory of Prof S Aime (University Torino).Methodological issues of the design and testing of CA that will be addressed in this project are:1) optimisation of the internalisation,2) specificity of the enzyme activity for the activation of the CA and3) maximisation of the generated contrast (increased sensitivity).CAs will first be tested on in vitro differentiated cultures of embryonal stem cells (L1 and D3 mouse stem cells) and then in animal models. Animal models utilised for the implantation are normal rats and models developed in the host laboratory for stroke and tumour. As the concept is universally applicable for visualisation of cell differentiation, it will improve high resolution in vivo monitoring of cell function also for models in other organs, other disease models and replacement therapy in humans. Fields of science natural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicineneurologystrokeengineering and technologymedical engineeringdiagnostic imagingmagnetic resonance imagingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Call for proposal FP6-2002-MOBILITY-12 See other projects for this call Funding Scheme IRG - Marie Curie actions-International re-integration grants Coordinator MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V. EU contribution No data Address Hofgartenstrasse 8 MUNICH Germany See on map Links Website Opens in new window Total cost No data
