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 #Dinaciclib molecular weight randurls[1|1|,|CHEM1|]# medicine is the iPSC. In 2006, Yamanaka and 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 17-DMAG (Alvespimycin) HCl 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.