The Wire

Of Mice and iPS Cells

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Shinya Yamanaka of Kyoto University in Japan first described induced pluripotent stem (iPS) cells in 2006. Since that initial landmark study, the true pluripotency of iPS cells has been a major unresolved question. “The most stringent test of pluripotency, the generation of live animals, could never be achieved” states Dr. Gerhard Bauer, laboratory director of the good manufacturing practice (GMP) facility for stem cell production at the University of California at Davis. “For this reason,” says Bauer, “iPS cells were often thought to be somewhat inferior to the gold standard embryonic stem cells and some scientists even doubted their usefulness.” Two new reports now demonstrate that iPS cells can indeed make a full mammalian body.

In the study by Zhao and colleagues at the Institute of Zoology in Beijing and Shanghai Jiao Tong University ¹ the authors created iPS cells using viral vectors to introduce the four “Yamanaka factors”: Oct4, Sox2, Klf4, and c-Myc. A “tetraploid” embryo was created in parallel by fusing two cells of an early-stage fertilized embryo, which after implantation develops into a placenta but lacks the embryonic cells needed for full body development. iPS cells were injected into the tetraploid embryos. Twenty days subsequent to implantation, a mouse named Xiao Xiao or “Tiny” was born; the animal was black like the mice used to create the iPS cells and not white like the mice used to create the tetraploid embryo. DNA tests confirmed that the mouse had arisen from iPS cells. The team of researchers injected 624 tetraploid embryos with iPS cells, of which 22 resulted in live births (a 3.5% success rate). Kang and colleagues at the Chinese Academy of Medical Sciences used the same approach as Zhao and colleagues to generate mice from iPS cells. ² These researchers transferred iPS cells to 187 tetraploid embryos, of which 2 resulted in live births (a 1.1% success rate). Both groups are now examining why most of the iPS cell lines were not successful in making mice.

These two studies are important, because as Bauer notes, they suggest that iPS cells are true pluripotent cells that “may in the future allow individualized tissue repair and replacement strategies that will reduce suffering and will save countless lives. Further collaboration of both the gene therapy and stem cell community will be needed to make the approach safe and ready for human applications.” Bauer cautions, however, that “new ethical debates will in all likelihood be generated by these accomplishments.” (sk)