Objective Background: To bypass hardware-related complication there have been substantial efforts to create biological pacemakers. Effective strategies have been identified and are now being refined for delivery of long-term function and clinical application. Yet, currently developed biological pacemakers only provide pacing to atrium or ventricle thereby aiming at ~20% of pacemaker patients. To unleash the full potential of biological pacing, targeting virtually every pacemaker patient, effective repair of atrio-ventricular (AV) conduction is crucial. With the arrival of advanced stem cell-based therapies, now is the time to meet this important challenge. Objective: To develop a stem cell-based therapy that restores impulse formation and conduction at the interface between atrium and ventricle.Approach: Human induced pluripotent stem cells (hiPSCs) will be used to produce cells with hallmark features of AV nodal cells. After in vitro testing, these cells will be implanted in vivo (together with biomaterials) to form AV bypass tracts in sheep that are in permanent AV block. In this setting, approaches will be tested for their ability to bridge electrical activity from the atrium to ventricle and protect the ventricle from atrial tachycardia. The final steps of this project focuses on the development of dedicated implantation catheters (in collaboration with Medtronic) and optimization of cellular constructs that are regulatory compliant and ready for clinical testing.Impact: By developing novel therapies to re-establish AV impulse formation and conduction I will broaden the application area of biological pacing to nearly all patients. In Europe ~300.000 pacemakers are implanted annually representing cots of ~8 billion Euros. Five per cent of these implantations result in serious complications requiring re-implantation or other invasive treatments. Biological pacemakers are expected to reduce these complications, improve quality of life, and reduce healthcare costs. Fields of science medical and health sciencesclinical medicinecardiologycardiovascular diseasescardiac arrhythmiamedical and health sciencesmedical biotechnologycells technologiesstem cellsengineering and technologyindustrial biotechnologybiomaterials Keywords Cardiac arrhythmias Biological pacing AV-node regeneration Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-STG - ERC Starting Grant Call for proposal ERC-2016-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Net EU contribution € 1 499 995,00 Address MEIBERGDREEF 15 1105AZ Amsterdam Netherlands See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 995,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Netherlands Net EU contribution € 1 499 995,00 Address MEIBERGDREEF 15 1105AZ Amsterdam See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 995,00