PLN CARDIOMYOPATHY

Graphical abstract

ABSTRACT

Patient-specific human Induced Pluripotent Stem Cells (hiPSC)-derived cardiomyocytes (hiPSC-CMs) hold great potential in in vitro disease modelling. Recently, in vitro research using hiPSC-CMs has focused on finding molecular mechanisms to understand PLNR14del pathophysiology. These studies suggested a role of an elevated unfolded protein response and disturbed metabolic function that resulted in decreased contractility. However, to our knowledge, the link between contractility, calcium handling and the profound amount of fibrosis found in the hearts of PLNR14del patients remains unknown.

Therefore, in this project, we aim to elucidate the molecular mechanisms related to the PLNR14del phenotype in a 3D context, by using human Cardiac Organoids (hCOs). The hCOs technology allows a robust middle-high throughput screening for novel therapeutic strategies to cure the PLNR14del disease.

Figure: Immunofluorescent imaging of Cardiac Organoid.

Video: Calcium imaging of a beating Cardiac Organoid.