![]() Before generating clinical-grade iPSC clones, all aspects of the donors, such as their health conditions and the type of human leukocyte antigen (HLA) expressed, can be examined. Fortunately, a major advantage of the iPSC technology is the diversity of donor candidates and ease of access to the cells of origin. It is therefore important to consider the use of allogeneic iPSC lines for regenerative medicine. In addition, because more than 3 months are needed to generate iPSCs using the current methods, the effective treatment of some disorders, such as spinal cord injury, cannot be achieved within the necessary timeframe. Realistically, however, using autologous iPSCs from each individual would be associated with high medical costs. Compared with allografts from other donors, the iPSC-based autologous method is advantageous in that the risk of immunological rejection, transmission of unidentified viruses or other forms of infection is negligible ( Araki et al., 2013 Guha et al., 2013). This was a perfect model for iPSC-mediated regenerative medicine: diseases caused by single gene defects can be addressed by made-to-order gene replacement in autologous cells. Gene correction by homologous recombination in a mutant iPSC line, followed by transplantation into mutant mice, cured the disease. In 2007, the proof of concept of the therapeutic use of iPSCs was reported for the mouse model of sickle-cell anemia, a genetic blood disorder caused by a defect in the β-globin gene ( Hanna et al., 2007). Nuclear reprogramming demonstrated that not only do somatic cells retain all genetic information, but they can also be rejuvenated by artificial manipulations to again acquire pluripotency. In parallel, it was previously believed that unnecessary genetic information was deleted or terminally inactivated in cells committed to a specific state, a theory known as Weismann's barrier ( Weismann, 1893). This is often depicted by the ‘epigenetic landscape’ proposed by Conrad Waddington ( Waddington, 1957) ( Fig. Before his breakthrough, differentiation had long been considered to be a one-way street, with traffic flowing from an immature state, a stem or progenitor cell, to a more mature differentiated state. His remarkable study demonstrated that the oocyte can completely reverse the acquired memories of somatic cells. In groundbreaking work, Sir John Gurdon succeeded in generating cloned frogs by transferring the nucleus of a tadpole's somatic cell into an oocyte ( Gurdon, 1962) ( Fig. However, as the proverbial phrase goes, ‘Rome wasn't built in a day’ and in fact the foundations of this field go back over 50 years. The recently developed induced pluripotent stem cell (iPSC) technology, which enables the induction of pluripotency in mature somatic cells by treatment with defined factors, has created new avenues in basic research, disease modeling and regenerative medicine ( Takahashi and Yamanaka, 2006). All cells that exist in the body, both somatic (of all three germ layers) and germ cells, originate from the pluripotent cells of the embryo. ![]()
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