New research led by the Heather group at the University of Oxford, UK, in collaboration with several EU-METAHEART members, has developed a model of “human diabetic cardiomyopathy in a dish”.
Changes in the heart muscle occur early during the development of type 2 diabetes and predispose to the development of heart failure with preserved ejection fraction. Metabolic changes are universally seen in preclinical and clinical studies of the diabetic heart. However, we currently don’t know what causes the cardiomyocyte changes in metabolic diseases such as diabetes, and have limited treatment options available. Therefore, human-centric cardiac models are needed for understanding disease progression and developing new therapies for type 2 diabetes.
In the newly published paper in Diabetes, scientists have used human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CM) in both 2D and 3D as engineered heart tissue (EHT), to produce a model of diabetic cardiomyopathy in cellulo. Taking an unbiased systems biology approach, they have shown that the model recapitulates the dysregulated pathways and functional derangements in the diabetic myocardium. Furthermore, using diabetes treatments they have shown improvements in cardiomyocyte function and metabolism in cellulo.
Professor Lisa Heather at the University of Oxford, UK comments “this new model of “diabetic cardiomyopathy in a dish” allows us to start unpicking disease mechanisms in a human centric manner, something that until now has not been possible as access to human cardiac biopsies early during disease development is not feasible”
This work was facilitated by the collaborative network generated by COST ACTION EU-METAHEART.