Transformation to Inducible Pluripotent Stem Cells

Since the discovery of embryonic stem cells (ESCs) in 1981, they have been used as a gold standard for stem cell therapy. However, the generation of ESCs requires the destruction of an embryo, making the use of these cells ethically controversial. ESC therapy is also hampered by immune rejection of ESC-derived allografts. In 2006, Shinya Yamanaka and colleagues developed an innovative protocol whereby somatic cells could be reprogrammed and dedifferentiated into a pluripotent state by transduction of four transcription factors, providing scientists with an alternative to overcome the ethical and immune rejection issues posed by ESCs. Since the breakthrough, numerous groups have developed various protocols to generate these induced pluripotent stem cells (iPSCs). However, the original protocol used to generate iPSCs involves the use of retrovirus, which can lead to genomic integration of virus genome into the host genome and can be a potential obstacle for future clinical translation of iPSC-based regenerative medicine. Recent rapid development of this field has introduced modified protocols to generate iPSCs using non-integrative techniques with increasing efficiency. These new developments have brought us one step closer to developing a safe and efficient method to reprogram cells for clinical use and shall be discussed in this chapter.