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Jan 2017 DOI 10.14302/issn.2574-4372.jesr-16-1395
Calcium (Ca2+) plays a central role in regulating many biological processes in the cell from muscle contraction to neurotransmitter release. The need for reliable fluorescent calcium indicator dyes is of vast importance for studying many aspects of cell biology as well as screening compounds using phenotypic high throughput assays. We have assessed two of the latest generation of calcium indicator dyes, FLIPR Calcium 6 and Cal-520 AM for studying calcium transients (CaTs) in induced pluripotent stem cell (iPSC) -derived human cardiomyocytes. FLIPR Calcium 6 and Cal-520 dyes both displayed robust CaTs with a high signal-to-noise ratio (SNR) and were non-toxic to the cells. The analysis showed that CaT amplitudes were stable between measurements, but CaT duration was more variable and tended to increase between reads. Two methods were compared for drug-screening hit-selection; difference in average (unstandardized) and standardized difference. The unstandardized difference was better for assessing CaT amplitude, whereas standardized difference was equal to or better for assessing CaT duration. In summary, FLIPR Calcium 6 and Cal-520 are suitable dyes for drug-screening using iPSC-derived human cardiomyocytes.
Jul 2017 DOI 10.14302/issn.2574-4372.jesr-17-1705
Drug-induced cardiotoxicity is one of the predominant reasons for drug attrition and withdrawals. This is of critical concern when potentially cardiotoxic drugs are administered to individuals with inherited arrhythmogenic cardiac diseases or with metabolic diseases such as obesity and diabetes, which are key risk factors for cardiovascular diseases. Pathophysiological alteration prevalent under such conditions can alter or exacerbate cardiotoxic responses. The growing incidence of obesity, diabetes and metabolic syndrome subject a significant percentage of the population to drug treatments, thereby augmenting their risk for drug-induced cardiovascular toxicity. Hence, screening for drug-induced cardiotoxicity early in the preclinical stages of drug development, by using appropriate human disease models, can be effective in ensuring safety in clinical trials and preventing late stage and post-marketing drug withdrawals owing to cardiotoxicity. The advent of human pluripotent stem cells (hPSC) and induced pluripotent stem cell (iPSC)-derived cardiomyocytes are revolutionizing safety/toxicity screening in human cells by providing relevant human-specific, renewable model systems to explore human drug toxicity. The ability to generate patient-specific iPSCs that can model cardiac diseases, now offers a valuable option that can further improve drug safety assessments and enable a more accurate prediction of toxicity that occurs in the representative population that are prescribed the drugs. Use of appropriate disease models will not only provide cost savings by decreasing potential drug attrition and withdrawals, seen with many drugs, but will also be a promising option to advance precision medicine
Jul 2016 DOI 10.14302/issn.2574-4372.jesr-16-1055
Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.