| Resumen: |
Diabetes is a complex disease that is frequently linked to increased risk of different complications that shorten life quality and lifespan in affected subjects. The main characteristics of the disease are caused by metabolic derangements, particularly in carbohydrates and lipid management, due to impaired insulin signaling. In this context, diabetic cardiomyopathy (DCM) is a subclinical manifestation of cardiac disease that silently progresses in subjects with diabetes. Organoid technology has upsurged in recent years, providing a powerful three-dimensional platform of human cardiomyocytes that structurally and functionally mimic human myocardium, enabling deeper insights into complex biological mechanisms. In this work, we aimed at setting up the culture conditions to develop cardiac organoids from iPSCs to explore the metabolic impact of diabetic mellitus (i. e. , increased palmitic acid (PA), glucose, or both) in this setting. Our data showed that cardiac organoids expressed gene targets that are characteristics of myocardium. Gene expression analysis demonstrated the presence of ventricular and atrial markers, suggesting incipient cardiac modeling. Moreover, they exhibited a beating rate at baseline, as revealed by their spontaneous electrophysiological response and calcium transient amplitude. Interestingly, the exposure to voltage and beta-adrenergic stimuli in matured cardiac organoids compared to those at early stages of differentiation; however, such physiological behavior was not accompanied by concomitant changes in gene expression of structural and metabolic molecular targets. On the other hand, the exposition of cardiac organoids to increased glucose or PA concentrations did not modify the gene expression of cardiac-specific and metabolically-related molecular targets. In conclusion, we developed functional cardiac organoids in vitro to study cardiac remodelling and physiology. On the other hand, the established diabetic conditions did not lead to concomitant changes in the differential expression of molecular targets involved in carbohydrate and lipid metabolism. |
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