Tandem research may herald way around embryonic stem cell dilemma

Conversion makes adult skin cells act very much like embryonic cells

Researchers in Japan and the United States, in simultaneous and nearly identical findings, may have doused one of the most heated controversies in health science research by discovering a way to transform adult human skin cells into cells that closely resemble and act like embryonic stem cells. If their work lives up to the promise indicated in the announcement made in November, the need for embryonic stem cells — and the emotional fight over their use — may evaporate, ethicists say.

Japanese researchers, who announced their findings in an early release publication of the journal Cell in November, said their process converts skin cells into cells that have many of the physical, growth, and genetic features of embryonic cells, and can differentiate to form other tissue types, including heart and nerve tissue.1 Scientists at the University of Wisconsin-Madison (UW-M), using a nearly identical process to yield the same results, announced their findings in the journal Science at the same time the Japanese team reported their findings.2

The "induced pluripotent stem cells" (iPS) are very close — though not identical — to embryonic stem cells, the researchers say. The Japanese research team used the same recipe to produce iPS cells from adult mouse cells a year earlier, they said.

Shinya Yamanaka, of Kyoto University in Japan, said in statements accompanying his team's report that the findings mark a hopeful step in finding an alternative to embryonic stem cells, but added that it is too soon to tell if iPS cells will completely replace embryonic cells.

Besides ethical objections, the use of human embryonic stem cells poses practical challenges in that it is difficult to generate patient-specific or disease-specific embryonic stem cells. One way to circumvent these issues is to induce pluripotent status in other cells of the body by direct reprogramming, Yamanaka said.

R. Alta Charo, JD, a UW-M professor of law and bioethics, says the scientific findings by UW-M researchers and in Japan could have far-reaching effects on the progress of stem cell research.

"This is a method for creating a stem cell line without ever having to work through, at any stage, an entity that is a viable embryo," Charo says. "Therefore, you manage to avoid many of those debates with the right-to-life community."

Yamanaka says using his research, science should now be able to generate patient- and disease-specific iPS cells, and then make various cells, such as cardiac, liver, and neural cells.

"These cells should be extremely useful in understanding disease mechanisms and screening effective and safe drugs," he adds. "If we can overcome safety issues, we may be able to use human iPS cells in cell transplantation therapies."

The Japanese research team includes scientists from Kyoto University in Japan and the Gladstone Institute of Cardiovascular Disease in San Francisco.

Findings affect cloning, funding

The new source of iPS cells also resounds in the area of cloning research. Charo says it means researchers can make customized, pluripotent cell lines without having to create an intermediate embryo that is a "clone" of an adult person.

In fact, when the Japanese research was announced, University of Edinburgh reproductive biologist Ian Wilmut, who cloned "Dolly" the sheep and is considered the pioneering leader of cloning, announced he would abandon cloning in favor of the cell conversion technique developed in Japan.

Wilmut, in a statement released shortly after the iPS announcements, says his decision is not motivated by ethics as much as evidence that the cell conversion approach holds better chances for success.

Ethicist David Stevens, MD, MA, CEO of the Bristol, TN-based Christian Medical & Dental Associations, hailed the announcements by the U.S. and Japanese researchers — as well as Wilmut's change of direction — as good news on both ethical and practical levels.

"This is very good news, because for those clinical trials using adults cells for 70 something diseases, this will give those interested in embryonic cells a relatively cheap, easily obtainable source of cell lines," says Stevens. "Labs can start up this week doing it. It opens up the research door, and without the ethical restrictions, there will be federal dollars available to do it."

Charo says the cell conversion findings may throw into question government funding for traditional embryonic stem cell research, which has been a political hot potato for some time. The Bush administration has twice vetoed legislation that would overturn its ban on embryonic stem cell research.

The discovery is likely to expand avenues of research that are already eligible for federal funding because they do not involve embryonic cell lines.

"This takes care of all the ethical issues that many have been concerned about," predicts Stevens. "It might be easy to say that ethical objections [to embryonic stem cell use] just involve a vocal minority, but when we get down to it — when you reach the point where embryonic stem cells are available for use in treatment — you would have 25 to 30% of the population saying, 'I can't do this; it's morally wrong.'"

References

  1. Takahashi K, Tanabe K, Ohnki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; doi:10.1016/j.cell.2007.11.0. Available on-line at http://images.cell.com (accessed 11/26/2007).
  2. Yu J, Vodyanik M, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; doi: 10.1126/science.1151526. Abstract available on-line at www.sciencemag.org (accessed 11/26/2007).

Sources

For more information, contact:

  • David Stevens, MD, MA, CEO, Christian Medical & Dental Associations. 2604 Highway 421, Bristol, TN 37620. Phone: (423) 844-1000.
  • R. Alta Charo, BA, JD, Warren P. Knowles Professor of Law & Bioethics, University of Wisconsin School of Law. 975 Bascom Mall, Room 8108, Madison, WI 53706. Phone: (608) 262-5015.