Application of Embryonic Stem Cells as a Novel Tool in Drug Screening

Abstract

Toxicological screening using animals are necessary for drug development registration. This approach is time-consuming, costly, labour intensive, stressful for the animals and susceptible to inaccuracies due to individual differences between animals. So, the screening of candidate chemicals in early development is often replaced with in vitro cell culture systems (Pearson, 1986; Liebsch & Spielmann, 2002). In vitro studies using cell lines were capable of providing more rapid, precise, relevant information than some animal studies, and economical approach for the evaluation of the pharmaco-toxicological profiling of target drugs, characterised by a low compound requirement and short duration (Pearson, 1986; Kari et al., 2007). Also, it is possible to include mechanistic studies, and to test for toxicity that is specific to humans: sensitivity differences between humans and rodents can affect animals (Kari et al., 2007). Among the in vitro screening systems, primary cell cultures and/or target organ-specific cell lines can be used to measure the general toxicity of a test compound (Zhou et al., 2006). However, the sensitivity of hepatotoxicity using primary human hepatocytes or the HepG2 cell line cannot predict effects in early development and toxicological differences, which depend on the state of differentiation in hepatocytes (Knasmuller et al., 2004; Xu et al., 2004). In addition to, primary cells such as hepatocytes in particular and many transformed human hepatocyte-derived cell lines (immortalized cultures, i.e Fa2-N4 cells, HepaRG cells) have limitations in their life span and can have donor-dependent variations (Mills et al., 2004). Also, they have disadvantages such as discontinuous phenotypic characteristics, functional properties and genetic instability. Therefore, more promised future is waiting for hepatocyte-like cells as the source of hepatocytes regarding the approach of stem cells use in the high throughput testing (Duret et al., 2007). Stem cells are defined functionally as cells that have the capacity to self-renew as well as the ability to generate differentiated cells that specialized functions in specific tissues and make up the organ (Thomson et al., 1998; Zhang & Wang, 2008; Schnerch et al., 2010). The classification of stem cells divided into embryonic stem cells (ESCs) and adult stem cells (ASCs) according to derivative origins. ESCs, which are derived from the inner cell mass of blastocysts after fertilization, can unlimited self-renewal and have pluripotent could be rise to cells derived from all three germ lineages. Otherwise, ASCs derived from the specialized cell types of the tissue from which are originated have limited self-replicate and mutilpotent could be giving rise to specialized cells into multiple-lineages not all three germ lineages.