About this Research Topic
Heart failure is the number one killer and drug induced cardiotoxicity is a major cause of market withdrawal. The lack of availability of culture systems for human heart tissue that is functionally and structurally viable for more than 24 hours limits validation of novel heart failure therapies and reliable cardiotoxicity testing. Therefore, there is an urgent need to develop reliable platforms for culturing human heart cells/organoids/tissue slices for testing drug efficacy and toxicity.
The recent move toward the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) in cardiotoxicity and drug efficacy testing has provided a potential solution to address this issue; however, the immature nature of the hiPS-CMs and loss of tissue integrity compared to multicellular heart tissue are major limitations of this technology. Recent efforts were focused on inducing maturation in hiPS-CMs for more reliable testing. Taking in consideration that heart tissue is structurally more complicated, being composed of a heterogeneous mixture of various cell types including endothelial cells and various types of stromal fibroblasts linked together with a unique mixture of extracellular matrix proteins. There are recent efforts to use hiPS-CMs based microtissues or organoids mixed with different types of supporting stromal cells. Additionally, recent developments for culturing human heart slices is a promising model of intact human myocardium. In this Research Topic, we aim to cover some of the most recent developments in various human based platforms that allow cardiac toxicity and pharmacological efficacy testing.
Original and Review articles are sought in the following general categories:
• Novel approaches to cardiotoxicity testing
• Novel platform technologies for pharmacological testing of cardiac therapeutics
• hiPS-CMs based toxicity and pharmacological platforms
• Organoid based toxicity and pharmacological testing.
• Heart slice platform for cardiotoxicity and efficacy testing
• Incorporation of studying molecular mechanisms for cardiotoxicity
• Using these human heart model systems to study human variability in response to pharmacological and toxic substances
• Disease modeling and pharmacological screening for novel pharmacological agents
• Use of gene ontology information to link adverse key events to biological and disease outcomes in human heart cells/organoids/tissue slices.
• Changes in regulation of toxic substances in the US according to the new models for drug testing.
Keywords: Heart, cardiomyocytes, drug, pharmacology, toxicity
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