Despite improved treatment, diabetes remains a chronic disease with major health risks and heavy burden on patients and society. Serious forms are caused by depletion in pancreatic beta cells and associated loss in insulin’s homeostatic control throughout life. Their cure requires restoration of a metabolically adequate beta cell mass. Implants of beta cell grafts prepared from human pancreases have shown proof-of-principle but also the need for developing a large-scale source for therapeutic cells. Our objective is to generate a functional beta cell mass by stem cell-derived implants in diabetes patients. A combined preclinical and clinical project will search recipient and implant conditions for formation and maturation of beta cells in subcutaneous implants of device-encapsulated pancreatic endodermal cells that are derived from human embryonic stem cells (hu-ES) and manufactured for clinical studies. We collected preclinical evidence for the therapeutic potential of this implant from comparison with clinically used human beta cell grafts. State-of-the art methods and markers have been developed to investigate the biology of implants and to monitor host immune and innate reactivity. This approach helps understand the basis for metabolic outcome and identify targets for improvement. Pilot studies examine the influence of the (auto)immune status of the patients. Data will determine transition to clinical efficacy studies, or indicate the need for further laboratory development. Implants in preclinical models will guide modifications in clinical protocols, and explore the biologic properties of grafts derived from human induced pluripotent stem cell (iPSc) as can also be prepared from diabetes patients. Our consortium joins innovating cells, methods, markers and minds in a unique combination of expert clinical, academic and industry activities that need each other to make progress in an ambitious program.

Metabolic disorders are at pandemic levels. Based on recent estimates, ~50% of Europeans are overweight, 20% are obese and 10% have type II diabetes. Obesity and insulin resistance impact European health to the tune of €110 billion per year. These disorders have genetic, nutritional and lifestyle causes. However, the molecular mechanisms that link nutrients and lifestyle to gene activity and chromatin are poorly understood, and drug targets are only starting to be identified. Pioneering experiments by ChroMe labs now reveal how sugars, exercise, the gut microbiome and novel drugs regulate chromatin. These novel links promise to substantially improve our understanding and treatment of metabolic disorders. National governments and the EU invest major resources to address the burden of the “metabolic syndrome”. However, there is an urgent need for expert human capital able to dissect metabolic diseases, exploit new targets and establish innovative therapies. No local nor international program currently provides adequate training at this emerging interface of chromatin and metabolism. ChroMe establishes a timely and intersectorial ETN that exploits Europe’s strengths in epigenetics, physiology and medicine to translate our molecular knowledge of chromatin–metabolism interactions into therapies. Our ESRs receive advanced training in emerging technologies, bioinformatic and translational approaches, and all engage in collaborative PhD projects co-supervised by academia and industry. ChroMe’s extensive transferable skills, dissemination and public engagement program equips our ESRs with the experience and personal network needed for a career in metabolic health. By systematically involving the non-academic sector at every level in our research, training and management, ChroMe will craft future European leaders with the necessary knowledge and skills to fight the metabolic syndrome pandemic.