The Past, Present and Future of Induced Pluripotent Stem Cells

Our body is derived from only one cell, a fertilized egg. At the birth, the body consists of 220 kinds of somatic cells. The fertilized egg divides many times during development. The resulting cells differentiate into many kinds of somatic cells, and a fertilized egg can differentiate into all of the different types of cells, including intraembryonic and extraembryonic tissues. This ability is called totipotency. Fertilized eggs differentiate into various kinds of somatic cells. However, somatic cells do not divide and differentiate into other types of somatic cells after differentiation in a disorderly manner. There are two possibilities to explain this. First, somatic cells can completely lose their potential to differentiate into other kinds of cells during development, or second, they may retain their potential, but such potential may be suppressed after development. The studies to elucidate how these processes occur were the origin of reprogramming science and regenerative medicine. In 1938, Spemann was the first person to carry out nuclear transplantation, but the experiment failed (Spemann, 1938). In 1952, Briggs and King transplanted the nucleus of a frog blastula into enucleated unfertilized eggs. The eggs developed into tadpoles. This was the first cloned animal with nuclear transplantation, and the origin of the cloning technique. An interesting discovery was that the later the nucleuses were taken during the developmental stage, the lower the efficiency of generating clone frogs. It was impossible to produce a cloned frog using the nucleus from a stage later than the development of a tailbud. At that time, they thought the information in the nucleus changed during development (Brigge & King, 1952). However, Gurdon arrived at a different conclusion from Briggs and King. He transplanted the nuclei of small intestinal epithelial cells into enucleated unfertilized eggs and obtained tadpoles (Gurdon, 1962). His data suggested that the nucleus of a somatic cell could be reprogrammed, and thereby regain the ability to differentiate into many kinds of cells. In 1997, the cloning of a sheep demonstrated that mammalian somatic cells could also be reprogrammed (Wilmut, 1997). These data suggested that the information in the nucleus did not change irreversibly during development, and indicated that somatic cells have the potentially ability to differentiate into other kinds of cells after development.