Ekiden to iPS Cells

Abstract

When I started a long ekiden—a relay marathon by multiple runners—toward cellular reprogramming about a decade ago, not many teams joined the start of the race. At the time, many laboratories were trying to differentiate embryonic stem (ES) cells into various functional cells, inspired by the report on the isolation of human ES cells1. In contrast, I tried to dedifferentiate somatic cells back to the embryonic state. I was not sure if we could reach our goal in my lifetime, but thanks to diligent colleagues and students in my laboratory (Fig. 1), luck favored us. In August 2006, we announced the generation of ES cell–like stem cells by introducing four transcription factors—Oct3/4, Sox2, Klf4 and c-Myc—into mouse fibroblasts by retroviral vectors2. I named this new type of cells ‘induced pluripotent stem (iPS) cells’. We reported the generation of human iPS cells3 on 20 November 2007, the same day that James Thomson and his colleagues also announced their success in making human iPS cells4. With the ability to differentiate into virtually all types of cells and to grow robustly like ES cells, iPS cells have enormous potential for pharmaceutical and clinical applications5,6. The technology is expected to be used for generating disease models, drug screening, toxicology and regenerative medicine, circumventing two obstacles surrounding ES cells—the ethical controversy over destruction of embryos to isolate ES cells and the risks of immune rejection when ES-derived cells are transplanted into a person. In vitro uses of iPS cells are just around the corner, but there are still many hurdles before their clinical application. However, I believe that strenuous efforts of researchers around the world will make the promises a reality in the not-too-distant future. Today, iPS cell research has become one of the hottest areas in the life sciences, with an increasing number of laboratories worldwide working on the technology. Many new findings have been reported in the short time since the first report was published5,7. I cannot stress enough that without the many studies using mouse and human ES cells that have appeared since the isolation of mouse ES cells in 1981 (refs. 8,9), we would not have been able to generate iPS cells and advance the field at such rapid speed. In fact, my encounter with mouse ES cells led me to start the ekiden toward iPS cell generation.