Addressing Variability and Heterogeneity of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Induced pluripotent stem cells (iPSCs) offer great promise in the areas of disease modeling, basic research, drug development, and regenerative medicine. Much of their value comes from the fact that they can be used to create otherwise inaccessible cell types, such as cardiomyocytes, which are genetically matched to a patient or any other individual of interest. A consistent issue plaguing the iPSC platform, however, involves excessive variability exhibited in the differentiated products. This includes discrepancies in genetic, epigenetic, and transcriptional features, cell signalling, the cell types produced from cardiac differentiation, and cardiomyocyte functionality. These properties can result from both the somatic source cells and environmental conditions related to the derivation and handling of these cells. Understanding the potential sources of variability, along with determining which factors are most relevant to a given application, are essential in advancing iPSC-based technologies.