Obiettivo Human embryonic stem cells, and embryonic-like induced pluripotent stem cells made from adult human skin, can differentiate to form beating cardiac muscle cells (cardiomyocytes). These stem cell-derived cardiomyocytes (SC-CM) are being investigated for use in cardiac repair, but also as a model system for research or drug toxicology. Their human origin, stability in culture and ability to be easily genetically modified in culture makes them far superior to present sources. Immediately after differentiation, SC-CM have the characteristics of immature foetal or neonatal cells in terms of contraction, growth and intracellular signalling. To realize their full potential, they need to grow towards the adult cardiomyocyte in these respects. We have evidence that this occurs in culture, over time-frames of 3-6 months, and that reproducing the stimuli for maturation can produce or accelerate these changes. One key maturational stimulus is thyroid hormone, and the first part of the project will apply this to SC-CM. However, the foetus has evolved sophisticated mechanisms to protect itself from maternal thyroid hormone, to prevent premature development. Intrinsic enzyme systems and receptor expression levels carefully control the intracellular environment with respect to levels of T3, the active agent, to preserve the natural staged differentiation and maturation programme. Particularly, an enzyme called D3 keeps levels of T3 tonically low. In the second time we will investigate the synergistic effects of adding T3 and down-regulating D3 on the rate and extent of maturation of the SC-CM. In the adult, cardiac growth programmes in response to increased load (hypertension for example) have been classified as pathological, while that controlled by thyroid hormone has been defined as physiological. In the third time we will compare the characteristics of SC-CM after T3-induced growth with our previous findings on stretch- or catecholamine-induced growth. Campo scientifico natural sciencesbiological sciencescell biologycell signalingmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinetoxicologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Invito a presentare proposte FP7-PEOPLE-2010-IEF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IEF - Intra-European Fellowships (IEF) Coordinatore IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Contributo UE € 208 592,80 Indirizzo SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Regno Unito Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Tatjana Palalic (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
