Induced pluripotent stem cell-derived cardiomyocyte in vitro models: tissue fabrication protocols, assessment methods, and quantitative maturation metrics for benchmarking progress

The advent of human induced pluripotent stem cells (hiPSCs) and techniques to differentiate cardiomyocytes from them has opened a viable path to creating in vitro models of normal and diseased hearts, accelerating more predictive drug screening and therapeutic strategies for cardiac pathologies. Currently, hiPSC-derived cardiomyocytes (hiPSC-CMs) are more similar to fetal than adult cardiomyocytes, leading many in the field to explore approaches to enhance cell and tissue maturation. There are over 2,000 studies utilizing hiPSC-CMs in models composed of various combinations of cell and extracellular matrix components, using a plethora of differentiation protocols, culture formats, and methods for quantifying cardiomyocyte function. To assess the current state of this rapidly growing area, we systematically analyzed 300 studies using hiPSC-CM models for their selection of hiPSC lines, hiPSC-CM differentiation protocols, types of in vitro models, maturation techniques, and metrics used to..., Across over 2,000 studies utilizing hiPSC-CMs from 2016-2022, there exists high variability in differentiation protocols, maturation strategies, and assessment of cell or tissue functionality. To understand the nature of this variability, we systematically analyzed 300 studies using hiPSC-CM models and compiled data on hiPSC lines, hiPSC-CM differentiation protocols, types of 2D and 3D in vitro models, maturation techniques, and metrics used to assess hiPSC-CM functionality and maturity. Using a PubMed search for “(((induced pluripotent stem cells) OR (iPSC)) AND ((cardiomyocyte) OR (cardiomyocytes) OR (iPSC-CM) OR (iPSC-CMs) OR (induced pluripotent stem cell-cardiomyocytes) OR (induced pluripotent stem cell-CMs))) AND ((engineered heart tissue) OR (cardiac microtissue) OR (maturation) OR (mature))” we identified 846 potential publications for analysis. We eliminated publications focusing on atrial differentiation due to relatively limited published work in this space and focused our be..., , # Induced pluripotent stem cell-derived cardiomyocyte in vitro models: tissue fabrication protocols, assessment methods, and quantitative maturation metrics for benchmarking progress

[https://doi.org/10.5061/dryad.ksn02v7bh](https://doi.org/10.5061/dryad.ksn02v7bh)

The advent of human induced pluripotent stem cells (hiPSCs) and techniques to differentiate cardiomyocytes from them has opened a viable path to creating in vitro models of normal and diseased hearts, accelerating more predictive drug screening and therapeutic strategies for cardiac pathologies. Currently, hiPSC-derived cardiomyocytes (hiPSC-CMs) are more similar to fetal than adult cardiomyocytes, leading many in the field to explore approaches to enhance cell and tissue maturation. There are over 2,000 studies utilizing hiPSC-CMs in models composed of various combinations of cell and extracellular matrix components, using a plethora of differentiation protocols, culture formats, and methods for quantifying cardiomyocyte f...