Human pluripotent stem cells in drug discovery and predictive toxicology.
Human pluripotent stem cells are a biological resource most commonly considered for their potential in cell therapy or, as it is now called, 'regenerative medicine'. However, in the near future, their most important application for human health may well be totally different, as they are more and more envisioned as opening new routes for pharmacological research. Pluripotent stem cells indeed possess the main attributes that make them theoretically fully equipped for the development of cell-based assays in the fields of drug discovery and predictive toxicology. These cells are characterized by: (i) an unlimited self-renewal capacity, which make them an inexhaustible source of cells; (ii) the potential to differentiate into any cell phenotype of the body at any stage of differentiation, with probably the notable exception, however, of the most mature forms of many lineages; and (iii) the ability to express genotypes of interest via the selection of donors, whether they be of embryonic origin, through pre-implantation genetic diagnosis, or adults, by genetic reprogramming of somatic cells, so-called iPSCs (induced pluripotent stem cells). In the present review, we provide diverse illustrations of the use of pluripotent stem cells in drug discovery and predictive toxicology, using either human embryonic stem cell lines or iPSC lines.
Laustriat
Delphine
D
INSERM/UEVE U861, I-STEM, AFM, 5 rue Henri Desbruères, Evry 91030 cedex, France.
Gide
Jacqueline
J
Peschanski
Marc
M
D000328:Adult; D054316:Biomarkers, Pharmacological / Q000032:analysis* / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011379:Prognosis; D044968:Regenerative Medicine / Q000379:methods; D014116:Toxicology / Q000379:methods*
D054316:Biomarkers, Pharmacological