Summary:
Over the last 20 years there has been a rapid development in both human
embryonic (hESCs) and adult stem cell culture techniques that resulted in a
significant increase in stem cells availability for research and potential use
in cell therapies. Stem cells are divided into pluripotent and multipotent. The
differentiation potency of stem cells (pluri /multipotency) makes them
potentially attractive reagents for in vitro cytotoxicity and developmental
toxicity assays. Lately research has been directed towards the improvement or
replacement of many conventional models of toxicity screening with more
relevant human systems. The result of these investigations will contribute to a
better assessment of chemicals and drugs, to a better testing of potential
developmental toxicants, and prediction of the side effects of these chemicals
and drugs to vital organs such as the liver. The aim of this thesis is the
development of a system based on umbilical cord mesenchymal stem cells, as an
"in vitro hepatotoxicity model of drugs and new chemical substances." In this
context, we studied a set of mainly hepatotoxic substances, and calculated
their half maximal inhibitory concentration (IC50), as well as the system`s
prediction rates among calculated experimental values and the acute median oral
lethal dose (LD50) in silico data. In conclusion, the development of a stem
cells-based in vitro specific target organ/systemic toxicity model, may
contribute, in the near future, to a more reliable risk assessment of potential
drugs, to the reduction in the use of laboratory animals, and finally, to the
decrease of the drug discovery cost.
Keywords:
WJ-MSCs, HepG2, NIH 3T3, MTS Assay, NRU Assay