Combine the wet and dry ingredients: Mixing experimental and computational models for a deeper understanding of stem...

Knowledge in cardiac development, heart disease and drug-induced toxicity has steadily progressed for centuries, but the most recent decades have seen an explosion in technological advancements that have benefited cardiac research. In particular, the development of induced pluripotent stem cells (iPSCs) derived from accessible human adult tissues, as well as lineage-specific cell cultures differentiated from these iPSCs, has led to the rapid growth of the iPSC-derived cardiomyocyte (iPSC-CM) as a promising in vitro model. However, major differences in iPSC-CM phenotype have been observed across studies. This variability may be attributed to differences in cardiomyocyte differentiation protocols, maturation efficiency, or iPSC donor genetic background. While phenotypic heterogeneity is an important aspect of modelling a population as diverse as humans, it can also confound research study interpretation and reproducibility. Computational models of iPSC-CM physiology provide a potential avenue for assessing the mechanisms behind varied phenotypes and responses without sacrificing the valuable information this heterogeneity provides. Recently, new developments in the calibration of mechanistic models have aided in the generation of patient- or cell line-specific computational models, which hold potential in benchmarking iPSC-CM preparations. In this review, we summarize recent literature on iPSC-CM heterogeneity and computational model calibration, and we emphasize the utility of integrating computational ('dry lab') models with information from experimental ('wet lab') datasets in future iPSC-CM studies.