These allogeneic cells are easier to procure and amenable to tissue banking. Nevertheless, the limitations of adult stem/progenitor cells provide a rationale for deriving therapeutic cells from other sources. A third type of stem cell that has remarkable potential for regenerative medicine is the iPSC. In 2006, Yamanaka and MLN8237 clinical trial colleagues4 reported that mouse fibroblasts

could be reprogrammed into iPSCs by viral transduction of genes encoding four master regulators of pluripotency: octamer-binding Inhibitors,research,lifescience,medical transcription factor 3/4 (Oct 3/4) and SRY-related high-mobility-group (HMG) box protein-2 (Sox2), in combination with Krüppel-like factor 4 (Klf4) and c-Myc.4 Successful reprogramming of adult human fibroblast cells into human iPSCs based on defined transcription factors has been reported independently by Yamanaka (Oct 3/4. Sox2, Klf4, c-Myc)5 and James Thomson (Oct4, Sox2, Nanog, Lin28).6 Human iPSCs are potentially Inhibitors,research,lifescience,medical better alternatives to human embryonic

stem cells (hESCs) because they can be patient-specific Inhibitors,research,lifescience,medical and avoid the political and ethical dilemmas surrounding hESCs.5, 6 Human iPSCs are already having a substantial impact on cardiovascular medicine, and their potential for regenerative cardiovascular therapies Inhibitors,research,lifescience,medical is promising. How iPSCs are Changing Medicine: Their Use in Modeling Cardiovascular Diseases Because somatic cells from any individual can now be induced into pluripotency, it is possible to make disease-specific cell lines from our patients. Thus, we can create “disease-in-a-dish” models with iPSC technology. Using iPSC-derived cardiovascular cells, investigators have already generated new insights into the molecular mechanisms of inherited cardiovascular diseases. Elegant studies have been reported using iPSC-derived cardiomyocytes from patients with Inhibitors,research,lifescience,medical long

QT syndrome, 7, 8 LEOPARD syndrome,9 and Timothy syndrome10 in vitro. Exemplary of this approach is the work of the Dolmetsch group, which reprogrammed human skin fibroblasts Non-specific serine/threonine protein kinase from Timothy syndrome patients to generate human iPSCs and differentiated these cells into cardiomyocytes. Electrophysiological recording and calcium imaging studies of the iPSC-derived cardiomyocytes revealed that the cells manifested irregular electrical activity and contraction, with abnormal calcium transients and prolonged action potentials. If the “disease-in-a-dish” model faithfully recapitulates the cardiovascular disease of the patient, then it may become a useful tool to determine if a drug has the potential to exacerbate the condition or to uncover new therapeutic avenues.