Harvard scientists have created cells similar to human embryonic stem cells without destroying embryos, a major step toward someday possibly defusing the central objection to stem cell research.

The team showed that when a human skin cell was fused with an embryonic stem cell, the resulting hybrid looked and acted like the stem cell. The implications: It may eventually be possible to fashion tailor-made, genetically matched stem cells for patients using such a cell fusion technique, rather than by creating and then destroying a cloned embryo. That use of early embryos is the main sticking point for opponents of stem cell research.

The Harvard researchers cautioned that the fusion technique, described in the journal Science, is inefficient and deeply flawed at this point, and emphasised that it should not deter embryonic stem-cell research that involves embryos, nor diminish support for such research. “Our technology is not ready for prime-time yet,” said Kevin Eggan, the paper’s senior author and an assistant professor at Harvard. “Our results do not offer an alternative now.”

The paper comes amid debate in Congress over whether the US government should expand its financing for research on embryonic stem cells, which are seen as potential treatments for a range of diseases such as Type 1 diabetes and Parkinson’s. Eggan said he feared that his work could be cited by opponents who have argued for finding ways of doing stem cell research without using human embryos. “The timing is complicated and I worry about it,” Eggan said.

The work is part of a broader effort to find ways to conduct embryonic stem-cell research without destroying embryos, a quest spurred by politics but driven mostly by the needs of scientific inquiry. There is a limited supply of human eggs, which are needed for creating embryos through cloning, and egg donors face a slight health risk. The new cell fusion technique would enable scientists to create vastly greater quantities of embryonic stem cells for research.

That would mean they could do far more experiments aimed at understanding what happens when a regular, adult cell is transformed into an embryonic stem cell, a process known as “reprogramming.” Researchers are struggling to determine how a cell that is “adult,” already committed to its role in the body as, for example, a nerve cell or skin cell, regresses back to the proto-state in which, as a stem cell, it could still potentially become any of the hundreds of types of cells in the body. The cell fusion technique “provides an experimental tool,” said Azim Surani, a Cambridge University professor who performed similar cell fusion in mice and was not involved with the Eggan paper. “It’s not something that we can use now, but it allows us to take steps toward understanding this process of reprogramming.”

To make an “adult” cell regress to an embryonic stem-cell state without needing an egg cell to do it “is what a lot of scientists dream about being able to do,” he said. “It opens up many different avenues in terms of doing basic research.”

The Harvard paper showed that the cell fusion would work in humans, and went further, showing exactly how extensive the “reprogramming” is ? that virtually all genes went from having a skin cell pattern to having an embryonic stem-cell pattern. Under a microscope, the fused cell looked like an embryonic stem cell. It could turn into many different types of cells. And it had the chemical markers of embryonic stem cells.

Real version: Korean scientist Hwang Woo-Suk, of Seoul National University, has already cloned embryos for stem cell research

“We’ve taken back a cell that had only one choice, a specialised function, and we’ve given it back the power to make many different choices, like an embryonic stem cell,” said Chad Cowan, the paper’s lead author. All the cells of your body have the same DNA, but there is a system, called “epigenetics,” that turns some genes off and on. This is what distinguishes a skin cell from another type of cell. And this is what must be “reprogrammed” to change the cell type.

In cloning, scientists use an egg cell to do the reprogramming. That is, a nucleus from a skin cell is put in an egg cell that has had its nucleus removed. Something in this egg cell changes the DNA around so that the new nucleus now thinks it’s a fertilized egg, and begins to develop.

Ultimately, using cell fusion could work better than using an egg for human stem-cell therapy, Surani said. But for now, gigantic obstacles remain. The most crucial flaw in the fused cell was that it contained twice the genetic material that cells usually carry, and there is no known way to return it to normal. Such cells would be extremely risky to use for therapies in humans, though they could be valuable for research.

Eggan said he planned to explore ways to solve the problem of the extra genes. It could be possible to pull out the extra DNA before the fusing process is complete.

Another option may be to reprogramme the skin cell using the stem cell’s cytoplasm, the area of the cell that is outside the nucleus where DNA is concentrated.

The other great obstacle to the cell fusion technique is its inefficiency. When Cowan was creating the fused cells, he found that about 50 million skin cells and 50 million embryonic stem cells would yield only 10 or 20 of the fused hybrid cells. Fortunately, he said, the resulting hybrid cells were stable and could be multiplied in culture.

The work was funded by the Naomie Berrie Diabetes Center, the Howard Hughes Medical Institute, and the Harvard Stem Cell Institute. It used a line of embryonic stem cells created by Harvard’s Doug Melton, but some of the work was repeated with an officially approved stem-cell line so that other researchers, who depend on government funds, would be able to try to replicate it.

If researchers manage to understand reprogramming well enough, Cowan said, it may someday be possible to use drugs to induce, for example, a pancreas cell in a diabetic patient to go back in time to its stem-cell state and transform itself into the kind of pancreas cell that makes the much-needed insulin.

But that, he said, is still science fiction. In the nearer future, the cell fusion technique offers the prospect of the kind of “limitless supply of human embryonic stem cells” that could allow researchers to forge ahead toward figuring out reprogramming. “You can now start to figure out the pieces of that puzzle, through biochemistry and genes,” he said. (NYTNS)