Present state and future perspectives of using pluripotent stem cells in toxicology research

Abstract

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed.

Assessment of Bisphenol A (BPA) neurotoxicity in vitro with mouse embryonic stem cells

“…Moreover, ESCs can virtually differentiate specifically into any type of cells of an adult organism. Those cells can then be used for cell function toxicity assays as any other derived primary cell type (Wobus and Loser, 2011;Liu et al, 2013;Mori and Hara, 2013).…”

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

“…The tests conducted in animal models are not yet well standardized. Apart from this, the animal models are not good representative of humans because inter-specific differences exist in accordance to pharmacokinetics and toxicokinetics background [5]. It often gives doubtful results during early (preclinical) or necessary late (clinical) assessment of newly synthesized drugs leading to termination of drug development programs (Fig.…”

The cytoprotective and the dark side of Nrf2

“…Further influential articles published in the Archives of Toxicology in recent years focus on nanotoxicity (Kim et al 2012;Landsiedel et al 2012;Nunes et al 2012;Trpkovic et al 2012;Gebel 2012;Oesch and Landsiedel 2012), the use of stem cells in toxicology (Wobus and Löser 2011;Krug et al 2013;Seiler et al 2011), carcinogenesis (Bernstein et al 2011Golka et al 2011;Burns and Korach 2012;Pavanello and Lotti 2012;Brambilla et al 2011), metal toxicology (Chasapis et al 2012, neurotoxicity (Soderlund 2012;Carvalho et al 2012;Mariussen 2012), in silico and in vitro methods (Karp and Caspi 2011;Godoy et al 2013;Mehling et al 2012;Geenen et al 2012) and oxidative stress (Matés et al 2012). The editors hope that this choice meets the current needs of our readers, and encourage them to suggest further In 1988, Paul Talalay and colleagues described a protein with highly reactive cysteine residues that protects against chemical carcinogenesis (Talalay et al 1988) This led to the discovery of an elaborate network of highly inducible, cytoprotective proteins that are controlled by the Keap1-Nrf2 pathway (Itoh et al 1999;Dinkova-Kostova et al 2002;Kobayashi et al 2004;Wakabayashi et al 2004;Motohashi and Yamamoto 2004;Zhang and Hannink 2003;Balogun et al 2003;McMahon et al 2003;Zhang et al 2004;Kwak et al 2003).…”