Alternative approaches to the derivation of ESCs from the ICM of pre-implanted embryos are now available and these tend to avoid ethical issues. Such methodologies directly generate pluripotent stem cell lines from differentiated adult somatic tissue and include nuclear transfer, cell fusion or direct reprogramming (Hochedlinger and Jaenisch, 2006). In 2006, a landmark discovery was published by the Yamanaka group at Kyoto University as they induced the expression of only four pluripotency-associated transcription factors, Oct3/4, Sox2, c-Myc, and Klf4 (OKSM), in mouse fibroblast cells resulting in the generation of ESC-like cells, called induced pluripotent stem cells (iPSCs). These cells are similar to the ESCs in their morphology, gene expression, proliferation and teratoma formation (Hochedlinger and Jaenisch, 2006; Takahashi and Yamanaka, 2006; Takahashi et al., 2007; Wernig et al., 2007; Hadadeh et al., 2012). These iPSCs are now widely used for various applications, such as autologous cell therapy, monogenic and multigenic diseases modeling, and as substrates for drug, toxicity, differentiation and therapeutic screens.
