The Magazine

The End of the Stem-Cell Wars

A victory for science, for the pro-life movement, and for President Bush.

Dec 3, 2007, Vol. 13, No. 12 • By RYAN T. ANDERSON
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That expectation has now been shattered. Whether or not the next president shares Bush's pro-life convictions, it is highly unlikely that taxpayer funds will go to support embryo destruction, which has become not only unnecessary but also less efficient than the alternatives. That's the story coming out of Cell and Science.

In Cell, Yamanaka announces that the pluripotent stem cell-producing technique he used on mouse cells works with human cells. The resulting cells--called induced pluripotent stem cells, or iPS cells--are functionally identical to human embryonic stem cells: They possess all of the same properties. The difference is simply in the method of their production.

This new production technique is possible because the difference between a stem cell and an adult cell is not a matter of genetics but of epigenetics: which genes are expressed, how, and to what degree. Different cells have the same genes, expressed differently. So scientists had been searching for a way to remodel the gene expression of adult cells to transform them into stem cells. Yamanaka's team discovered a collection of four genes--Oct3/4, Sox2, Klf4, and c-Myc--that does precisely this. When introduced into adult cells, these genes directly reprogram the cells to a pluripotent state.

I asked Maureen Condic, professor of neurobiology and anatomy at the University of Utah School of Medicine, about these cells. "Direct reprogramming of adult cells to pluripotent stem cells is one of the most significant scientific findings of the last quarter century," she said. "This approach holds tremendous promise for advancing our scientific understanding of stem cells and for advancing the study of regenerative medicine. However, there are concerns regarding the safety of iPS cells for human therapies, due to the use of viral vectors that integrate into the cell's DNA, potentially causing dangerous mutations, and to the use of c-Myc, a gene that is associated with some forms of human cancer."

Yamanaka himself notes these pitfalls, but indicates that they should be surmountable: His technique works even when you take c-Myc out of the mix and use only the other three genes (though it achieves its results at a less efficient rate). Moreover, Yamanaka notes that integration of the virus into the DNA will not reduce the usefulness of induced pluripotent stem cells for study of human diseases in the laboratory, and that other nonviral means of introducing the reprogramming factors into cells are likely to be sufficient to generate iPS cells.

The Thomson approach described in Science avoided some of these drawbacks by using no c-Myc and optimizing the safety of the induced pluripotent stem cells from the start. His team used a different group of genes--Oct4, Sox2, Nanog, and Lin28--to achieve the same end: direct reprogramming of adult human cells to the pluripotent state. Thomson's technique is also noteworthy because it uses a lentivirus to introduce the gene group, which is the safest of retroviral integration methods. Work still needs to be done to ensure that viral vectors do not introduce dangerous mutations, but the scientists I spoke with thought this would be achievable with minimal delay.

What does all of this mean? James Thomson explains it best in his Science paper:

The human iPS cells described here meet the defining criteria we originally proposed for human embryonic stem cells, with the significant exception that the iPS cells are not derived from embryos. Similar to human embryonic stem cells, human iPS cells should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine. For transplantation therapies based on these cells, with the exception of autoimmune diseases, patient-specific iPS cell lines should largely eliminate the concern of immune rejection.

In short: The new technique produces patient-specific stem cells with all the benefits of stem cells from embryos, but without the production and destruction of human embryos or the use of human eggs.

Because induced pluripotent stem cells, created from a patient's own body, are a perfect genetic match, they should prove especially useful for both the study of diseases and the development of treatments. Thomson notes, "For drug development, human iPS cells should make it easier to generate panels of cell lines that more closely reflect the genetic diversity of a population, and should make it possible to generate cell lines from individuals predisposed to specific diseases."

Wilmut, of Dolly the sheep fame, agrees. Comparing his cloning methods with Yamanaka's, he said, "The work which was described from Japan of using a technique to change cells from a patient directly into stem cells without making an embryo has got so much more potential."