Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling

Abstract

The possibility to induce pluripotency in somatic cells or, even further, to induce cell transdifferentiation through the forced expression of reprogramming factors has offered new, attractive options for cardiovascular regenerative medicine. In fact, recent discoveries have demonstrated that induced pluripotent stem (iPS) cells can be differentiated into cardiomyocytes, suggesting that iPS cells have the potential to significantly advance future cardiac regenerative therapies. Herein, we provide an overview of the characteristics and differentiation potential associated with iPS cells. In addition, we discuss current methods for inducing their specification towards a cardiovascular phenotype as well as in vivo evidence supporting the therapeutic benefit of iPS-derived cardiac cells. Finally, we describe recent findings regarding the use of iPS-derived cells for modeling several genetic cardiac disorders, which have indicated that these pluripotent cells represent an ideal tool for drug testing and might contribute to the development of future personalized regenerative cell therapies.

Keywords: BMPs; Bone morphogenetic proteins; CMs; CPCs; CPVT; Cardiac differentiation; Cardiac progenitor cells; Cardiac regeneration; Cardiomyocytes; Catecholamine polymorphic ventricular tachycardia; Cell reprogramming; DMSO; Dimethylsulfoxide; ECs; END-2; ESCs; Embryonic stem cells; Endoderm-like cell line; Endothelial cells; FGF; Fetal liver kinase-1; Fibroblast growth factor; Flk-1; G-CSF; GSI; GSK3; Glycogen synthase kinase-3; Granulocyte colony-stimulating factor; Human embryonic stem cells; Human induced pluripotent stem; Induced pluripotent stem; Induced pluripotent stem (iPS) cells; Isl1; Islet-1; JAK–STAT; Janus kinase–signal transducer and activator of transcription; LIF; Leukemia inhibitory factor; MI; Myocardial infarction; OSKM; Oct3/4, Klf-4, Sox-2, and c-Myc; SCF; SMCs; Smooth muscle cells; Stem cell factor; Stem cell therapy; TGFβ; Transforming growth factor-β; VEGF; Vascular endothelial growth factor; hESCs; hiPS; iPS; γ-Secretase inhibitor.