Human Embryonic Stem Cells -- Without an Embryo

Scientists have imbued ordinary human skin cells with the versatile qualities of embryonic stem cells -- what some doctors call a scientific breakthrough that could change the tone of the ongoing stem cell research debate.

The advance was published in two independent studies reported in the journals Cell and Science on Tuesday.

The findings on the technique, known as "direct reprogramming," follow a study published last week in the journal Nature that reported the extraction of stem cells from cloned monkey embryos, which contained genetic material from adult monkey skin cells. And they come five months after a similar feat was accomplished in mice.

The technique has big implications for human stem cell research, as it sidesteps many of the ethical and political pitfalls that have dogged the field for years.

Now that the research has been done in human cells, the excitement in the stem cell community is mounting. And while it may not be the perfect solution, many say it's a major advance.

"The discovery that it is possible to reprogram adult human cells to pluripotency using a simple combination of genes is an important breakthrough," said Sean Morrison, director of the stem cell biology research center at University of Michigan, Ann Arbor.

"It represents a phenomenal breakthrough, more important than cloning … or the discovery of human embryonic stem cells," said Dr. Markus Grompe, director of the Oregon Stem Cell Center in Portland. "This is a Nobel Prize worthy advance."

Researchers led by Shinya Yamanaka at the Kyoto University in Kyoto, Japan, generated cells called "induced pluripotent stem cells" by inducing four different genes to hitch a ride into human skin cells within specially designed viruses. These genes incorporated themselves into the skin cells, transforming them.

The new cells displayed several characteristics of embryonic stem cells, including the ability to grow into nerve and heart cells.

Similar cells were generated from human skin cells by a team led by Dr. James Thompson at University of Wisconsin in Madison. Both of these teams used an approach that generated embryonic stem cell-like cells without using an embryo.

"This research seems to be very well done, and follows on the heels of similar work by the Yamanaka laboratory in mouse cells that was independently confirmed by other laboratories," Morrison said.

But even amid the excitement, several scientists cautioned against overinterpreting the results.

"It should be made clear that this amazing breakthrough will not produce immediate cures," Grompe said.

"The therapeutic potential of all human pluripotent stem cells, including those generated by direct reprogramming, remains uncertain."

Easing the Moral Dilemma?

The prospect of eliminating the controversial use of an embryo as a middle step to generate embryonic stem cell-like cells could well represent a holy grail of sorts to many in the scientific community whose research has been limited thus far.

"It is possible to generate human pluripotent stem cells by direct reprogramming, with good efficiency and without creating -- in other words, cloning -- or destroying human embryos," Grompe said. He added that the technique could also solve the problems associated with using hard-to-obtain eggs surgically harvested from women.

In a separate editorial published in Science, R. Alta Charo, a University of Wisconsin at Madison professor of law and bioethics, noted that this research could greatly affect the political and social controversy surrounding embryonic stem cells.

"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 commented in the editorial. "Therefore, you manage to avoid many of those debates with the right-to life community."

On a political level, Congress in the past has attempted to overturn Bush administration policies on embryonic stem cell research and expand funding on embryonic stem cell lines.

"It's going to fuel those who call for preferential federal funding only for nonembryonic stem cell research, and it will certainly complicate any efforts to expand funding for embryonic stem cell research at the federal level," noted Charo in the editorial.

The Catch

But there are other hurdles that stand between this advance and therapeutic use. Most significantly, researchers report an increased risk of cancer associated with stem cells derived through this approach. One reason for this increased risk seems to be the use of viruses as conduits to carry proteins into cells.

Thus, one of the most vaunted potential uses for stem cells -- the creation of new replacement tissues to treat conditions such as diabetes, Parkinson's and spinal cord injury -- is still beyond the horizon.

"The risk for cancer -- a feature common to all pluripotent stem cells -- is a major problem and this risk may be higher in these cells than in embryo-derived stem cells because the viral genes used for reprogramming remain present in the cell," Grompe said.

Regardless, this approach holds great promise for further research.

"Pluripotent stem cells can be used to study developmental biology in a dish -- i.e., to observe how human cells, organs and tissues form," Grompe said. "The insights obtained from such studies are likely to lead to the development of new drugs and strategies which can benefit human health."

This approach holds potential for generating stem cells from specific individuals and specific diseases like Parkinson's disease, Type 1 diabetes and leukemia, to name a few.

"Taking a human disease stem cell and showing that it makes a disease in a dish -- that says to the whole human race that now we'll be able to study disease in a dish and not wait for the progression of the disease in patients," said Dr. Doug Melton, co-director of the Harvard Stem Cell Institute in Boston.

Wire reports contributed to this story.