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Dr Matthias Stadtfeld, Assistant Professor at the New York University School of Medicine and Dr Kejin Hu, Assistant Professor at University of Alabama at Birmingham, discussed the potential of stem cells for medical research and drug discovery.
Relevance of iPS cells in cell based screening and drug development
Drug development requires highly validated, reproducible, consistent and predictive models in order to quickly validate key targets and assess toxicity in pre-clinical assays. High quality human iPSC cells can help to that direction and Nick Clare analyses further in his presentation at ELRIG Drug Discovery 2017 how that can be achieved.
We presented 'in the field' data on our portfolio of human iPSC and primary cells demonstrating their proven ease of use, reliability and consistency as meaningful drug discovery tools. Here, we overcome the challenges of cell line variability and address the needs for cell scale-up in assay campaigns.
Toxicologists have access to a range of iPSC-derived cell types, including cardiomyocytes, hepatocytes and renal cells, used in toxicity screening. We discuss how these models are accurate and representative cell models, and how they can phase out inconsistencies and reduce the use of in vivo models.
Axol Bioscience specialize in the supply of human cell culture systems and custom services for disease modeling and drug discovery. Our expertise includes induced pluripotent stem cell (iPSC) generation, CRISPR-Cas9 gene editing, iPSC differentiation and custom cell and tissue sourcing.
We offer a variety of functionally validated human primary cells and human iPSC-derived cells from both healthy and patient donors alongside culture media and reagents that are tailored to support the optimal growth and maturation of our cells. This enables you to carry out your project in a physiologically relevant system that is not only reliable and easy to use but produces consistent results for robust replication studies.
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The innovation of human iPS cells has revolutionized the field of drug discovery and development, offering researchers access to a consistent and almost infinite supply of stem cells from a single donor source. Human iPSC-derived cells can offer a more physiologically relevant model to be used for screening candidate drugs. Human iPSC-derived renal proximal tubular cells are an example of a new cellular development that would be ideal for use in drug discovery to identify and predict drug induced toxicity.
The development of the first pre-validated screening platforms for accurate prediction of nephrotoxicity in humans, and the potential applications of these cells within drug discovery and toxicology with progression to future kidney-on-chip technologies for dose response prediction.
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.
Currently, the majority of studies on Alzheimer's disease have used transgenic animal models or imaging studies of the human brain. It is difficult to validate these findings using human tissue. Whilst animal models have been central to our understanding of human physiology, human stem cell-based models may help us to further our understanding of human physiology and tackle devastating diseases such as Alzheimer's disease.