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Arch Hellen Med, 33(1), January-February 2016, 8-21


The use of stem cells in the establishment of drug toxicity models

K. Katsaounou, E. Taki, V. Zoumpourlis
Biomedical Applications Unit, Institute of Biology, Medical Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece

Over the last 20 years there has been a rapid development in both human embryonic (hESCs) and adult stem cell culture techniques resulting in a significant increase in the availability of stem cells for research and potential use in cell therapies. Stem cells are classified into pluripotent and multipotent cells. The differentiation potency of stem cells (pluri-/multipotency) makes them potentially attractive for in vitro cytotoxicity and developmental toxicity assays. Recent research has been directed towards the improvement of many conventional models of toxicity screening or their replacement with more relevant human systems. This will result in enhanced drug toxicology prediction and enable the testing of potential developmental toxicants, which cannot be investigated in humans, because of bioethical issues. Human induced pluripotent stem cells (iPSCs), which are generated by reprogramming somatic cells into hESC-like cells, may be useful in elucidating the genetic and environmental factors that contribute to individual responses. This can be achieved by the establishment of in vitro toxicity models, created from individuals with a diverse range of drug susceptibilities, resistance or disease. The comprehensive profiles of hESC and iPSC cells and their complicated biochemical pathways of physiological response to drugs can be successfully clarified utilizing recent advances in the fields of genomics, proteomics, metabolomics and transcriptomics. In this way, the everincreasing use of stem cell based in vitro toxicity models aims at: (a) Reduction of the number of animals used in toxicity testing, (b) improvement of risk assessment and drug biological response studies, and (c) development of more efficient, large-scale and low-cost models for the production and testing of new drugs.

Key words: Cytotoxicity, Developmental toxicity, Embryonic stem cells (ESCs), Induced pluripotent stem cells (iPSCs), Mesenchymal stem cells (MSCs), Stem cells.

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