Three-dimensional mature cardiac microtissues from human induced pluripotent stem cells to explore mitochondrial dynamics, cardiac function and therapeutic options in Friedreich Ataxia

Myocardial energy production is significantly impaired in Friedreich ataxia patients, and this reduction may even precede the development of tissue damage in the heart. These investigators have recently found that the shape of mitochondria, which is crucial for their function, is altered in isolated Friedreich ataxia patient cells and can be restored by genetically increasing the levels of the mitochondria-shaping protein OPA1. In this project, they will use an innovative tool, cardiac microtissues or “mini-hearts,” obtained from patient stem cells to investigate 1) if remodeling of the mitochondrial shape can correct cardiac dysfunction and 2) if increasing the levels of frataxin can correct the mitochondrial and cardiac defects. Modeling cardiac dysfunctions in Friedreich ataxia is a crucial and challenging task, and cardiac microtissue is an advanced cellular model that will allow us to mimic more closely the human myocardium. Defining the molecular features of the disease in an appropriate cellular context will facilitate the development of novel therapeutic strategies for Friedreich ataxia.