1. Date of download: 6/24/2016 Copyright © The American College of Cardiology. All rights reserved. From: Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine J Am Coll Cardiol. 2016;67(18):2161-2176. doi:10.1016/j.jacc.2016.01.083 Potential Applications of Patient-Specific iPSCs Disease-specific target cells differentiated from patient-specific induced pluripotent stem cells (iPSCs) have 3 major applications: disease modeling, regenerative therapies, and drug discovery/toxicity studies. iPSCs from patients with genetic mutations could be corrected via genome editing to yield healthy target cells for cell therapy. Both corrected and uncorrected target cells could be used for disease modeling or drug screening. RBC = red blood cells. Figure Legend:

2. Date of download: 6/24/2016 Copyright © The American College of Cardiology. All rights reserved. From: Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine J Am Coll Cardiol. 2016;67(18):2161-2176. doi:10.1016/j.jacc.2016.01.083 Conventional Versus iPSC-Based Drug Discovery (A) The conventional drug discovery pathway is a very inefficient process with a high attrition rate. The majority of candidate drugs never reach the market because of safety and efficacy issues. This is attributable in part to the lack of appropriate drug development models that could accurately predict drug efficacy and in part to dependence on animal models of disease that do not replicate human pathophysiology. (B) By comparison, induced pluripotent stem cell (iPSC) technology allows high-throughput screening of therapeutic molecules by providing disease-specific drug development models that are generated from the patients themselves. This makes iPSC technology a much better predictive tool and enables well informed decisions to be made earlier in the drug development process. FDA = U.S. Food and Drug Administration; iPSC-CM = induced pluripotent stem cell–derived cardiomyocyte. Figure Legend:

3. Date of download: 6/24/2016 Copyright © The American College of Cardiology. All rights reserved. From: Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine J Am Coll Cardiol. 2016;67(18):2161-2176. doi:10.1016/j.jacc.2016.01.083 iPSC Clinical Trial: From Micromedicine to Macromedicine Induced pluripotent stem cell (iPSC) technology has contributed to both micromedicine and macromedicine. This includes everything from disease modeling and drug development based on cellular and molecular analyses of individual patients to iPSC clinical trials for stratification based on cellular and molecular analyses of a cohort of patients. Importantly, it could allow for the creation of a more precise clinical trial by identifying a subset of patients with a specific disease who optimally respond to the drugs under investigation, thereby boosting success rates by pre-selecting these drug responders. DNA = deoxyribonucleic acid; iPSC- CM = induced pluripotent stem cell–derived cardiomyocyte; RNA = ribonucleic acid. Figure Legend: