Objetivo Compelling evidence exists that somatic stem cell-based therapies protect the central nervous system from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis and stroke. It was first assumed that stem cells directly replace lost/damaged cells, but it has now become clear that they are able to protect the damaged nervous system through mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke we have shown that transplanted NPCs possess a constitutive and inducible ability to mediate efficient bystander myelin repair and axonal rescue. Yet, a comprehensive understanding of the mechanisms by which NPCs exert their therapeutic impact is lacking. We envisage that major NPC functions would result from highly sophisticated horizontal communication and we attribute a key role to the transfer of secreted membrane vesicles (MVs) from NPCs to neighbouring cells. Here we will focus on defining whether this form of communication exists for NPCs, and on elucidating its molecular signature and therapeutic relevance. We will investigate the MV small RNAome using next generation deep-sequencing, computational analysis and bioinformatics tools; and demonstrate that ncRNAs from NPCs are able to affect gene expression in neighbouring cells. Functional readouts of candidate ncRNAs will be provided by semi-quantitative RT-PCR and cutting-edge molecular and cellular biology tools [eg., miRNA-regulated LV vectors; identification of ncRNA targets by quantitative proteomics] on recipient cells. Then, we will demonstrate the biological impact of the transfer of individual small ncRNAs in vitro and in vivo in rodents with experimental neurological diseases. The true innovation of this project relies in its unique peculiarity to look into an innate mechanism with the visionary focus of translating the knowledge of basal stem cell functions into innovative high clinical impact therapeutics. Ámbito científico natural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cells Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Convocatoria de propuestas ERC-2010-StG_20091118 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Aportación de la UE € 1 410 932,40 Dirección TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Reino Unido Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Renata Schaeffer (Ms.) Investigador principal Stefano Pluchino (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Reino Unido Aportación de la UE € 1 410 932,40 Dirección TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Renata Schaeffer (Ms.) Investigador principal Stefano Pluchino (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos EUROPEAN MOLECULAR BIOLOGY LABORATORY Alemania Aportación de la UE € 89 067,60 Dirección Meyerhofstrasse 1 69117 Heidelberg Ver en el mapa Región Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo de actividad Research Organisations Contacto administrativo Ratcliff Tom (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
