CAMEOS · Cardiac micro-engineered tissue for high-throughput screening

Cardiac micro-engineered tissue for high-throughput screening

Heart disease is the most significant cause of morbidity and mortality in the industrialized world, and the cause of 4 million deaths each year within the European Union. The prevalence of the disease is a huge burden on society estimated to cost the EU economy 60 billion annually on drug therapy, patient care, and loss in productivity. Nonetheless, despite the latest advances in research much remains to be learn about pharmacological treatments in cardiovascular disease. Recently, the ability to produce an unlimited supply of human cardiomyocytes (CMs) from induced-pluripotent stem cells (iPSC) has allowed researcher to study human heart disease in an unprecedented manner. The scalability of iPSC-CMs makes them amendable for high throughput screening (HTS) applications, in which the role of proteins and signaling pathway can be unraveled in context of CM physiological function. Furthermore, the creation of iPSC line from patients allows for the creation of ‘patient-in-a-dish” models. In this setting, HTS approach can applied to find novel therapeutic interventions and help in the development of individualized medicine. However, the limitation of the current format centers on the lack of phenotypic cardiomyocytes maturity (the iPSC-cardiomyocyte do not behave like cardiomyocyte present in the heart). Consequently, these in vitro models often fail to recapitulate relevant physiological traits. The aim of CAMEOS is to develop a culture media to enhance the physiological relevance for in vitro high-throughput screening application. This will be achieved by re-formulating key component of culture media, to offer the cells a more physiological relevant environment in order to promote their maturation. After the development of optimized culture condition, I will apply the developed media to model a complex disease mutation, phospholamban (PLN) R14del, for which the pathology is poorly understood and no cure is available. Finally, I will perform HTS in attempt to find novel therapeutic targets in the PLN-R14del patient iPSC-CMs.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз