Advances in Pluripotent Stem Cell-Based in Vitro Models of the Human Heart for Cardiac Physiology, Disease Modeling and Clinical Applications

Cardiovascular diseases (CVDs) are the leading cause of mortality in developed countries worldwide. Many cardiac disorders caused by genetic and/or environmental factors are characterized by cell death, inflammation, fibrosis and tissue remodeling leading to structural, electrical, and metabolic alterations.

The availability of appropriate and reliable in vitro models able to resemble the human heart is pivotal in cardiovascular research in order to increase our understanding of molecular mechanisms underlying cardiac (patho)physiology for the development of novel therapeutic approaches.

Therefore, the discovery of induced pluripotent stem cells (hiPSCs) and their differentiation potential into cardiovascular cell types brought new prospects for the development of advanced tools for disease modeling, drug discovery and personalized/regenerative medicine. Importantly, human iPSC-derived cardiac cells, carrying the genetic background of donor somatic cells, allow to investigate genotype-phenotype relationships in monogenic, complex and polygenic or genetically unknown conditions.

Although significant progress has been made, the development of novel approaches to mimic the cellular composition and complex architecture of human cardiac tissue remains an urgent need for generating physiologically relevant tissues for disease modelling, drug screening, and therapeutic repair.

The goal of this Research Topic is to collect state-of-the-art in vitro human cardiac systems enable to improve our understanding of cardiac physiology and diseases, providing more efficient tools for therapy development and personalized medicine. This collection will also provide insights into the future directions to develop more accurate models that best recapitulate the (patho)physiology of the human native tissue.

In this Research Topic, we encourage researchers to contribute with original research articles as well as reviews, methods, commentaries and perspectives from all the areas of stem cell-based cardiac biology, including but not limited to:

• Human stem cell derived cardiac in vitro models
• Pluripotent cell derived spheroids, organoids and engineered heart tissues
• Cardiac tissue engineering approach and organ-on-chip
• Cardiac cell-specific models (atrial, nodal, ventricular)
• Three-dimensional cardiac models for studying cardiac development/physiology
• Patient-specific cardiac model for disease modelling, personalized medicine and clinical application
• Complex in vitro human cardiac models for drug testing and cardiotoxicity
• Maturation of stem cell-derived cardiac cells
• Genome editing for establishing cardiac-specific reporter lines or correcting genetic mutations
• Optimization of differentiation and cell culture practices to achieve high reproducibility in hiPSC disease modeling

This Research Topic is part of the Experimental Models and Model Organisms series of Frontiers in Physiology. Other titles in this series include:

• Model Organisms and Experimental Models in Membrane Physiology and Membrane Biophysics: Opportunities and Challenges
• In Vitro Models: Opportunities and Challenges in Aquatic Physiology
• Experimental Models and Model Organisms in Cardiac Electrophysiology: Opportunities and Challenges
• Animal Models and Transgenic Technology in Craniofacial Biology
• Model Organisms and Experimental Models: Opportunities and Challenges in Vascular Physiology Research
• Model Organisms: Opportunities and Challenges in Developmental Physiology
• Invertebrates as Model Organisms: Opportunities and Challenges in Physiology and Bioscience Research
• Model Organisms and Experimental Models: Opportunities and Challenges in Musculoskeletal Physiology
• Model Organisms and Experimental Models: Opportunities and Challenges in Integrative Physiology
• Model Organisms and Experimental Models: Opportunities and Challenges in Redox Physiology
• Experimental Models of Rare Cardiac Diseases

Keywords: Human pluripotent stem cells (hPSCs), Three dimensional cardiac models, Cardiac spheroids/organoids, Engineered heart tissues, Cardiac development, Disease modeling, Cardiotoxicity, Drug testing, Personalized and precision medicine

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.