Figure 1.

Strategies for obtaining human disease-specific cardiac cells and their use in disease modeling and drug screening. Human embryonic stem cells (hESCs) can be derived from human normal blastocysts and then genetically targeted to introduce a disease-associated mutation by homologous recombination. Alternatively, patient-specific induced pluripotent stem cells (iPSCs) can be derived directly from patient somatic cells (e.g., skin fibroblasts or blood cells) by different reprogramming methods. Either type of disease-specific pluripotent stem cells can be differentiated in vitro into all kinds of cardiac cells (cardiac myocytes, cells of the conductive system, smooth muscle cells, and endothelial cells) through a cardiovascular progenitor population. Differentiated cardiac cells can then be used in disease modeling to understand the molecular mechanisms underlying disease phenotypes and in drug screening to determine the effects of candidate drugs or new compounds and identify target pathways. Examples of different cellular readouts are presented.