, 2007, Mateizel et al., 2006 and Mateizel et al., 2010). This scarcity of PGD stem cell lines is partly due to the small number of embryos discarded after PGD and to the fact that PGD is only routinely carried out for a select number of monogenic neurological disorders. Alternatively, disease-causing mutations can be introduced into human ES cell lines by homologous recombination (Urbach et al., 2004). Unfortunately, disease-specific PGD embryos, as a resource, are limited in number and producing disease-specific ES cell lines by homologous recombination

is highly inefficient. In addition, in both cases, these approaches do not allow for see more the modeling of sporadic disease or for correlations to be made DNA Damage inhibitor between in vitro cellular phenotypes and clinical observations made over the lifetime of the patient. Another approach for using hES cell lines for disease modeling is to genetically modify them to express a disease-causing transgene using cell-type-specific promoters (Karumbayaram et al., 2009a). However, this approach would again only be useful

for modeling monogenic diseases caused by highly penetrant mutations and not for modeling complex disorders for which genetic determinants are either unknown or poorly understood. In contrast, the “reprogramming” of somatic cells allows the production of induced pluripotent stem (iPS) cells, which possess all of the salient characteristics of ES cells. These iPS cells can be generated using readily accessible tissue from patients with any condition. The obvious advantage of such an approach is that patient-specific Polo kinase iPS cells carry the precise genetic variants, both known and unknown, that contributed to disease, residing in the context of the patient’s own genetic background. Thus, any cellular phenotypes

observed could be correlated with clinical benchmarks such as rate of disease progression. Additionally, patient-specific iPS cells may eventually serve as a customizable resource for personalized regenerative medicine, drug testing, and predictive toxicology studies. Since the initial derivations of patient-specific iPS cell lines (Dimos et al., 2008 and Park et al., 2008a), there has been a dramatic expansion in the number of diseases for which cell lines have now been created (Table 1). The approach of induced pluripotency by defined factors has emerged as an alternative method for the derivation of human pluripotent stem cells that overcomes many of the limitations associated with the derivation and manipulation of hES cells. In 2006, Shinya Yamanaka’s group demonstrated that the combined ectopic expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc was sufficient to reprogram mouse fibroblasts into what were termed induced pluripotent stem cells, or simply iPS cells ( Takahashi and Yamanaka, 2006).