Patient-Specific Induced Pluripotent Stem Cell–Based Disease Model for Pathogenesis Studies and Clinical Pharmacotherapy

There are several significant limitations to progress in studying cardiac disorders, including the lack of relevant tissue samples, inability to study human cardiomyocytes longitudinally, and lack of a patient-specific drug testing platform.1 Traditionally, researchers have relied on cell-based assays or animal models to understand disease progression and develop therapeutic interventions.2 However, these models have well-known limitations in reproducing human pathophysiology. In addition, such models fail to recapitulate the considerable genetic variation that exists within disease populations, which may play a role in dictating the extent of disease severity and spectrum of patient responses to medical therapy. Clinicians typically rely on a patient’s history, clinical examination, and test results to formulate a clinical diagnosis and choose the presumed appropriate pharmacotherapy. However, clinical diagnoses often fail to consider diversity in underlying causes that could lead to similar clinical presentations. Conventionally, patients with similar clinical presentations will still receive the same medications on the basis of their symptoms, ignoring patient-specific factors that may affect response to therapy.3 Therefore, there is a compelling need for better models to gain insights into patient-specific disease mechanism and clinical pharmacotherapy.4 See Article by Maizels et al The emerging human induced pluripotent stem cell (iPSC) technology has considerable advantages over classical models by overcoming limitations associated with other models of human disease. Because iPSCs can be derived from healthy versus diseased patients, they provide a robust alternative to animals for researchers to model human diseases.5–7 In addition, iPSCs are patient specific, allowing them to more faithfully recapitulate the genotype encoded by original donor; this enables researchers …