Modelling the XXXX with induced pluripotent stem cells.

@entity1 @entity1164 @entity943 @entity1372 @entity72313 @entity72312 @entity74 @entity460 @entity972 @entity1162 @entity9678 @entity855
The ability to generate @entity1 -specific @entity1 induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling @entity1 disease and for individualizing drug testing. @entity1162 ( @entity1162 ) is a @entity72312 characterized by abnormal ion channel function and @entity1164 . Here we report the development of a @entity1 /disease-specific @entity1 iPSC line from a @entity1 with type-2 @entity1162 (which is due to the @entity72313 missense mutation in the @entity9678 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in @entity1162 @entity1 iPSC-derived cardiomyocytes (the characteristic @entity1162 phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac @entity972 current I(Kr). Importantly, @entity1162 -derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered @entity943 . We then used the @entity1162 @entity1 iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate ( @entity972 -channel blockers) or ameliorate ( @entity460 -channel blockers, K( @entity855 )-channel openers and late @entity1372 -channel blockers) the disease phenotype. Our study illustrates the ability of @entity1 iPSC technology to model the abnormal functional phenotype of an @entity74 and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize @entity1 care (personalized medicine), and aid in the development of new therapies.
