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The ability to monitor cardiomyocyte beat rate in real time is a powerful tool for drug discovery research. To do this, human iPSC-derived cardiomyocytes (iPSC-CMs) were cultured in a non-invasive impedance monitoring system (xCELLigence®) to assess cardiotoxicity and cell contractility in a 96-well plate format.
Measuring the colony forming potential of endothelial colony forming cells (ECFCs) is an excellent method for identifying the toxic effect of a compound on the proliferative potential of ECFCs.
Many disease pathologies are exacerbated by damage to blood vessels whereas increased vascularization encourages cancer progression and tumour growth, therefore there is an increased need for drugs that can alter the proliferative population of circulating ECFCs. This application note highlights the relevance and suitability for Human iPSC-Derived ECFCs in the investigation for compounds that target the anti- or pro-proliferative capabilities of ECFCs.
Three key points were covered in this study: Firstly, whether Axol Human iPSC-derived ECFCs were able to form colonies in vitro that hold a hierarchy of proliferative potentials equivalent to human primary cord blood ECFCs. Secondly, the in vitro colony forming potential of hiPSC-ECFCs was compared with human primary umbilical cord blood (CB) ECFCs. Finally, the application of ECFCs in a toxicity screen which identified the susceptible ECFC population.
Human iPSC-derived cardiomyocytes: A comparison with primary cells and applications in standard and 3D culture models
The University Hospital Bern studies the mechanisms of cancer therapy-associated cardiotoxicity, and wants to study this in cardiomyocytes, thus they always endeavor to use the most relevant in vitro culture systems. Therefore, they have recently started to develop a 3D-culture model using hiPSC-derived cardiomyocytes and have tested this system in comparison with mature primary cells.
Induced pluripotent stem cell-derived endothelial colony forming cells offer a robust and physiologically relevant research tool
Human iPSC-Derived Endothelial Colony Forming Cells (ECFCs) (Axol Bioscience) are highly expandable and show comparable expression and functionality to primary cells, providing a robust and physiologically relevant tool for use in numerous applications. ECFCs are rare circulating endothelial cells that display a hierarchy of clonal proliferative potential and possess in vivo vessel-forming ability upon implantation. In numerous animal models of disease, human ECFCs have demonstrated the capacity to promote revascularization and reperfusion to injured vascular beds via direct integration and/or through paracrine effects.
Human umbilical cord blood is enriched in circulating ECFCs compared to adult peripheral blood. We have recently reported that ECFCs displaying properties similar to cord blood can be obtained from human ESCs and iPSCs. Using defined serum-free culture medium and sequential addition of specific growth factors, we’ve identified ECFC precursors within 12 days of iPSC differentiation. These iPSC-derived ECFCs display clonogenic proliferative potential and in vivo vessel forming ability similar to cord blood ECFCs and promote vascular repair and regeneration in multiple animal models of human disease.