Induced pluripotent stem cells: the new patient?

Abstract

Worldwide increases in life expectancy have been paralleled by a greater prevalence of chronic and age-associated disorders, particularly of the cardiovascular, neural and metabolic systems. This has not been met by commensurate development of new drugs and therapies, which is in part owing to the difficulty in modelling human diseases in laboratory assays or experimental animals. Patient-specific induced pluripotent stem (iPS) cells are an emerging paradigm that may address this. Reprogrammed somatic cells from patients are already applied in disease modelling, drug testing and drug discovery, thus enabling researchers to undertake studies for treating diseases 'in a dish', which was previously inconceivable.

Integrating cardiomyocytes from human pluripotent stem cells in safety pharmacology: has the time come?

“…Protocols are available to direct cell differentiation towards many somatic cell lineages, including CMs (Mummery et al , 2012; Schwach and Passier, 2016). Chemically defined media supplemented with developmentally relevant growth factors [or small molecules that activate similar pathways, (Burridge et al , 2014; Chen et al , 2014; van den Berg et al , 2016)] are now commercially available or sold as complete kits so that deriving CMs from pluripotent stem cells (as hESC‐CM or hiPSC‐CM) is now feasible for most laboratories.…”

“…Research over the last few years has increasingly documented the potential of hiPSC in replicating (genetic) cardiovascular disease phenotypes, monogenic cardiac channelopathies being among the most common class of diseases modelled (Bellin et al , 2012; Šarić et al , 2014). In addition, hiPSC‐CMs are also being used as model systems to test the effect of both known and novel drugs on cardiac channelopathies (Matsa et al , 2011; Zhang et al , 2012; Bellin et al , 2013; Di Pasquale et al , 2013; Zhang et al , 2014), with suppression of pathological pro‐arrhythmic potential and restoration of altered AP duration (APD) being two main endpoints.…”

Calcium signaling in human pluripotent stem cells

“…In addition, hPSCs can be generated with normal genetic background or with patient-specific mutations, depending on the starting cell populations [3,4]. Irrespective of the source and procedure they are generated, all hPSCs can be cultured practically for unlimited time in vitro, and have the potential to differentiate into all cell types (such as cardiomyocytes, hepatocytes, neural cell types etc.)…”

Stem cells: from biomedical research towards clinical applications

“…For example, patientspecific iPS cells harboring specific mutations are differentiated into mature fully functional cells, such as neurons, for toxicity studies and pharmacological testing [10]. Such studies combined with advanced organoid cultures [6,7] offer unprecedented opportunities for drug discovery and personalized medicine [10][11][12]. Further to this, stem cell growth and/or development can be aberrantly deregulated and thereby give rise to cancer stem cells [13].…”