The European Consortium for Communicating Stem Cell Research (EuroStemCell) unites 33 partner institutions, that collectively represent >400 stem cell research groupings across Europe. Our common goal is to provide trusted high quality information on stem cells accessible to citizens and stakeholders across Europe, through support and further development of the multi-lingual European Stem Cell Information Portal www.eurostemcell.org. To achieve our aims, EuroStemCell will adopt the highly structured system for coordinated information management established by the FP7 Coordination and Support Action (CSA) also called EuroStemCell. From this, we will implement an ambitious programme of online and direct stakeholder engagement with stem cell research and regenerative medicine, aimed at European citizens at all educational levels. This will include provision of resources tailored specifically for decision-making on stem cell-related questions and an extensive programme of dissemination and capacity building in science communications and public engagement. The proposed work centres on an information hub team, which will link to all project partners and to stakeholders in the stem cell and regenerative medicine arenas and wider society, working with these groupings to implement the project. All outputs will be delivered in 6 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading stem cell labs across Europe, including new member states, together with experts in ethical and societal concerns and evaluating clinical outcomes. It thus provides unparalleled European expertise across the fields of stem cell biology and regenerative medicine and is uniquely placed to maintain and further develop www.eurostemcell.org as a world-leading stem cell information resource, thus meeting the challenge outlined in Topic HOA-6-2014.

Alzheimer’s disease (AD) is an age-related chronic neurodegenerative disease with four main pathological changes in the brain: amyloid plaques, fibrillary tau tangles, inflammation and neuronal loss. Phagocytes around amyloid plaques in late onset AD (LOAD) may be neurotoxic but have limited motility and phagocytic activity, suggesting a dysfunctional activation. These phagocytes express the innate immune receptor TREM2 and CD33. Variants of both genes have been linked to LOAD. The main objectives of PHAGO are to find means of modulating microglia/macrophage activation via TREM2, CD33 and related signalling pathways, and determine the effects of such modulation on microglia/macrophage function, amyloid-β and neurodegeneration, in order to find a treatment for AD. PHAGO will deliver well characterized tools and knowledge through which to manipulate AD risk and provide targets and markers ready to progress to drug development. PHAGO will realise this goal by comprehensively attacking the problem simultaneously at multiple levels, including the molecular structures of the receptors, receptor ligand interactions, ectodomain function in vitro and in vivo, characterisation of receptor processing, modification and signalling, receptor-regulated signalling pathways, gene expression and phagocyte function in cells and animals, comprehensive analysis of receptor knock-in and knock-out models crossed to two different animal models of AD, and identification of receptor-related biomarkers in AD patients. Innovative approaches of PHAGO will include identification of new AD-risk genes using a TREM2 co-expression network approach, brain imaging of AD patients with TREM2 and CD33 variants, and generation of patient iPSC-derived microglia/macrophages to comprehensively phenotype gene variants. The project will also generate tools, such as ligands, reporter cells and optimised assays, suitable for further development of treatments targeting TREM2 and/or CD33 in AD.

Neurodegenerative diseases and brain injuries affect large patient groups and carry large unmet clinical needs. NSC-Reconstruct will respond to these needs by developing innovative therapies based on cell replacement, cell reprogramming and circuit reconstruction that have the potential to transform how we treat a wide range of neurological diseases and disorders. In this area of clinical science European research has generated groundbreaking knowledge that has resulted in a pioneering human embryonic stem cell-derived product that is now entering clinical trials for Parkinson’s Disease (PD). In NSC-Reconstruct we will move beyond the replacement of a single neuronal type towards future cell therapies with enhanced authenticity, functions and compositions. NSC-Reconstruct will address PD as an example of disorder for which single neuron replacement has been developed. Our focus in PD will be on incorporating improved cell types and on local network reconstruction. We will also work on repairing long distance networks such as those affected in Huntington’s disease and finally in restoring the complex networks and projections of the cerebral cortex to achieve effective repair in conditions known to affect this structure, such as trauma or stroke. NSC-Reconstruct will lead to (i) the generation of neuronal types with clinically relevant functionality starting from human pluripotent stem cells or through in situ reprogramming, (ii) the optimization of donor cell composition through grafting of functional modules comprising distinct cell types capable of forming appropriate connections, (iii) the restoration of function through the reconstruction of these damaged connections and finally (iv) a greater understanding of the immunogenicity of grafted cells and how this can be minimized. Ultimately, NSC-Reconstruct will provide unique knowledge and products that will pave the way for future CNS cell replacement therapies using functionally enhanced and immune-tolerant cells.