Book of abstract 2008

Stem cells in toxicology
Laura Gribaldo
ECVAM-IHCP-JRC, European Commission
Rapidly increasing knowledge of human stem cells offers the unique possibility to establish
in vitro toxicological methods in many different areas in which currently only primary cell
cultures, cell lines derived from animals or immortalized cells are used. Stem cells of different
sources can be used as “cell factory” for human cell based systems. However, the relevance
and reliability of such in vitro test systems is strongly correlated to the quality of the source,
i.e. the stem cells used, standardized differentiation protocols, the purification rate of stem
cells and their derivates, selected toxicological endpoints as well as the developed prediction
models. Hematopoiesis is a fascinating system in which pluripotent hematopoietic stem
cells (PHSCs) differentiate into many highly specialised circulating blood cells. At least
95% of hematopoietic cells fall into morphologically recognizable cell lineages. Dormant
PHSCs are recruited into the cell cycle by many cytokines as IL-1, IL-3, IL-4, IL-6, IL-11,
IL-12, SCF (stem cell factor), G-CSF (granulocyte-colony stimulating factor), M-CSF
(macrophage-colony stimulating factor), Epo (erythropoietin), LIF (leukemia inhibitory
factor), FLk2/FLT3 (tyrosine kinase receptor) ligand, TPO (thrombopoietin).
Lineage-specific factors support the survival, proliferation and maturation of progenitors
that are committed through hypothetical stochastic expression of specific groups of
differentiation genes. The foetal stem cells, for their plasticity, can generate a perpetual
supply of healthy, normal human cells for disease modeling, drug discovery, and toxicology,
because they can potentially generate suitable models for cardiotoxicity, hepatotoxicity,
genotoxicity/epigenetic and reproductive toxicology. Furthermore, gender-differences in
drug sensitivity can be evaluated using human hematopoietic stem cells from different
donors.
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