Physiol Rev. 2019 Jan 1;99(1):79-114. doi: 10.1152/physrev.00039.2017.

Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development.

Karagiannis P¹, Takahashi K¹, Saito M¹, Yoshida Y¹, Okita K¹, Watanabe A¹, Inoue H¹, Yamashita JK¹, Todani M¹, Nakagawa M¹, Osawa M¹, Yashiro Y¹, Yamanaka S¹, Osafune K¹.

Abstract

The discovery of somatic cell nuclear transfer proved that somatic cells can carry the same genetic code as the zygote, and that activating parts of this code are sufficient to reprogram the cell to an early developmental state. The discovery of induced pluripotent stem cells (iPSCs) nearly half a century later provided a molecular mechanism for the reprogramming. The initial creation of iPSCs was accomplished by the ectopic expression of four specific genes (OCT4, KLF4, SOX2, and c-Myc; OSKM). iPSCs have since been acquired from a wide range of cell types and a wide range of species, suggesting a universal molecular mechanism. Furthermore, cells have been reprogrammed to iPSCs using a myriad of methods, although OSKM remains the gold standard. The sources for iPSCs are abundant compared with those for other pluripotent stem cells; thus the use of iPSCs to model the development of tissues, organs, and other systems of the body is increasing. iPSCs also, through the reprogramming of patient samples, are being used to model diseases. Moreover, in the 10 years since the first report, human iPSCs are already the basis for new cell therapies and drug discovery that have reached clinical application. In this review, we examine the generation of iPSCs and their application to disease and development.