Induced pluripotent stem cells (iPSCs) can be generated by reprogramming of adult/somatic cells. The somatic cell reprogramming technology offers a promising strategy for patient-specific cardiac regenerative medicine, disease modeling, and drug discovery. iPSCs are an ideal potential option for an autologous cell source, as compared to other stem/progenitor cells, because they can be propagated indefinitely and are able to generate a large number of functional cardiovascular cells. However, there are concerns about the specificity, efficiency, immunogenicity, and safety of iPSCs which are major challenges in current translational studies. In order to bring iPSC technology closer to clinical use, fundamental changes in this technique are required to ensure that therapeutic progenies are functional and nontumorigenic. It is therefore critical to understand and investigate the biology, genetic, and epigenetic mechanisms of iPSCs generation and differentiation. In this spotlight paper the discovery, history, and relative mechanisms of iPSC generation are summarized. The current technological improvements and potential applications are highlighted along with the important challenges and perspectives. Finally, emerging technologies are presented in which improvements to iPSC generation and differentiation approaches might warrant further investigation, such as integration-free approaches, direct reprogramming, and the development of iPSC banking. 1. Introduction Myocardial infarction (MI) is an important manifestation of coronary artery disease (CAD) and major cause of death and disability worldwide. MI occurs when prolonged ischemia irreversibly destroys distal blood vessels and myocardium, causing apoptosis or cell death, eventually triggering cardiac remodeling or sudden death [1, 2]. Recurrent MI leads to chronic postinfarct heart failure in patients with a longer life span. Currently, traditional therapeutic approaches focus on limitation of the initial injury and secondary maladaptive complications in order to prevent the death of existing myocardium. Despite significant advances in medical treatments over the past decades, chronic heart failure remains as a leading cause of death [3, 4]. Indeed, heart transplantation is the only available viable therapeutic option for end-stage heart failure, but this option is limited by the paucity of matched donor tissue specimens and by the requirement for life-long treatment with immunosuppresive agents. Regenerative therapies offer great promise for patients with heart disease by using angiomyogenesis to create
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