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Cell Therapy - a promising research field of modern medicine

In order to be able to address the extremely wide variety of cell therapies, the project ENCITE has been divided into generic and disease-oriented objectives. Since the project start, first key objectives have been achieved thanks to a strong collaboration of 26 European institutes and three from Israel, with outstanding scientific expertise in imaging.

The mission of ENCITE is to develop and test new MR and optical imaging methods and biomarkers to get a more comprehensive picture of cell fate and the reaction of the immune system and to ultimately improve and further develop cell therapy for the benefit of the European patient. MR imaging methods for cell tracking based on iron oxides were successfully implemented, and clinical methodologies for preclinical evaluation of novel drugs were adapted and optimised. The image post-processing group generated 3D and 4D datasets from the brain and the heart, recorded under variable conditions using different MRI contrast and spatial resolutions. The aim was to evaluate the usefulness of the chosen imaging and image analysis strategies and to characterise the boundary conditions for successful image processing and analysis, including an articulated atlas for image registration of follow-up studies. The main results achieved within the project so far were the synthesis of iron oxide nanoparticles at gram scale and the synthesis and in vitro testing of an MRI reporter based on detection of beta-galactosidase activity. Preliminary experiments were successfully carried out regarding novel tools for cell labelling and cell fate imaging (recruitment, differentiation, and cell death). Initial cell labelling experiments indicated the ability of porphyrins incorporated in endosomal membranes to induce the endosomal escape of contrast media by UV irradiation of labelled cells. Another highlight is the successful construction of the Adenovirus TK vector. As for cell fate imaging, experiments showed that it is possible to image tumour stroma cell activation and differentiation by fluorescence intravital microscopy. In terms of pre-clinical validation, the main results related to neurological diseases were the design of paramagnetic CEST agents (Communications Exchange on Saturation transfer in Torino) with improved properties for cell labelling purposes. A transgenic mouse model was generated. The model reports on neurogenesis using a bioluminescent reporter allowing an increase in neurogenesis to be detected after stroke. The major breakthrough related to musculoskeletal diseases is the use of CEST to assess glycose-aminoglycan (GAG) concentration in the intervertebral disc, which may lead to early diagnosis of disc degeneration and a way to monitor repair mechanisms by stem cells. The main results in the translation towards clinical applications refer to cancer and diabetes: With respect to cancer, the clinical trials that incorporate imaging techniques were approved. In the DERMA-ER-DC 06 trial, several patients already demonstrated broad response to numerous peptides prior to vaccination. Furthermore, tetramer-based 8-colour flow cytometry has become a routine monitoring assay, allowing extended phenotypic and functional characterisation of T-cell subpopulations. The identification of polyfunctional T-cells was of particular interest, since these have been shown to elicit more effective immune responses in HIV vaccination trials. With respect to diabetes, a sequence for the measurement of high resolution MR images at 3T Imager Trio Siemens was developed. The position of labelled pancreatic islets was found to be visible as black spots. Publications and citations of publishable articles with details on these results are available at: www.encite.org > Press In the long-term, ENCITE should lead to extensive collaboration on the development of novel imaging tools and implementation at the level of translational medicine across Europe, leading to a significant global impact. In view of the results within novel imaging technologies, the consortium is confident of reaching the overall goal to provide novel imaging technologies and post-processing tools that will enable more efficient and sensitive diagnostic and scientific tools in the field of cell therapy. The consortium is highly encouraged to facilitate new and groundbreaking developments in the field of cell-based therapies. The methods being developed for novel tools for cell labelling could potentially improve monitoring of cell therapy. Through the validation and implementation of the developed imaging tools in pre-clinical settings, a better understanding of the fate of transplanted cells and of how cell-based therapies provide therapeutic benefit will be obtained, and tools for clinical monitoring of such therapies can be implemented. Through the knowledge obtained in these studies, treatment strategies can then be (further) optimised to reap full benefit of the therapeutic potential of cell-based therapies. The ENCITE consortium will organise the 2nd ENCITE Workshop from 21 to 22 May 2010. The programme will be designed and held by the ENCITE consortium and will include progress reports of the project as well as other major aspects and latest advances in the field of cell imaging and tracking.

Countries

Austria, Belgium, Bulgaria, Cyprus, Czechia, Germany, Denmark, Estonia, Greece, Spain, Finland, France, Hungary, Ireland, Italy, Lithuania, Luxembourg, Latvia, Malta, Netherlands, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia