Heart disease continues to be the leading cause of death worldwide. Our understanding of heart disease in humans is limited because human heart tissues are hard to come by. The human heart cells generated from stem cells can be used to grow human heart tissues in a dish. This pre-clinical human heart model has allowed us to test new drugs that have potential to protect the heart from injury, and to study genetic mutations that can cause heart disease.
Development of effective new drug candidates that are specific and effective for humans has been severely limited and detailed characterisation of human heart disease is urgently needed. However, this has been largely impeded by the limited access to viable human heart samples and by the cellular diversity of heart tissue. We have established a novel cardiac organoid model with an integrated vasculature and sympathetic neuronal network. We hypothesise that this multicellular human cardiac organoid constructed with human induced pluripotent stem cell derivatives can recapitulate the cellular and microenvironment changes during cardiac injury. This study will establish a pre-clinical human heart tissue model for cardiac disease modelling and drug development that will facilitate animal-to-human translation.
Stem cells have the potential to treat heart disease by producing beneficial soluble factors and membrane-bound particles. This project aims to accelerate the development of a new, safe and minimally invasive method to deliver the beneficial proteins of stem cells to patients, using a retrievable encapsulation device that protects the transplanted cells, to allow long-term treatment for effective cardiac repair.
Mitochondria are the powerhouses of cells. They are membrane-bound compartments, within the cell, that use nutrients to produce chemical energy to power the cell’s biochemical reactions. One of the processes involved in the heart damage is a change in the shape of the mitochondria. Mitochondria can either join together by the process of fusion or divide into smaller pieces by the process of fission. A protein called Drp1 is needed for mitochondrial fission and blocking Drp1-mediated mitochondrial fission can protect against heart damage. However, until recently, there has not been a specific and potent enough inhibitor of Drp1 that could be developed into an effective drug for humans. We have discovered new drugs that can bind specifically to the human Drp1, inhibit mitochondrial division and protect animals from heart damage after heart attack. In this project, we will continue to improve the potency and specificity of these new drugs for heart protection and repair.