Oct. 9 (Bloomberg) -- The researcher who pioneered a way to make powerful stem cells from bits of skin or other adult tissue has improved the technique to reduce the risk of cancer.

Shinya Yamanaka of Kyoto University reported a new method, described today in the journal Science, that uses a tiny ring structure called a plasmid to deliver genes into mouse cells and turn them into stem cells. The technique eliminates the need to use viruses, which can trigger cancer, to transform cells.

``This is a major advance,'' said George Daley, a researcher at the Harvard Stem Cell Institute and Children's Hospital in Boston, in an October 7 e-mail. ``Strategies that allow us to make cells that don't carry viruses move us closer to realizing a major goal of stem cell research -- delivering cells as medicines.''

Because of their versatility, stem cells have the potential to repair or replace damaged tissue in people with hard-to-treat conditions such as diabetes, Parkinson's disease and spinal cord injuries.

Yamanaka announced two years ago a method that used viruses to ferry genes into skin cells, endowing them with the same power as embryonic stem cells to become any cell type in the body. Since then, researchers have been trying to achieve the same result without viruses, which can permanently lodge in the DNA of the cell and trigger cancer.

In the newest method the plasmids, unlike viruses, didn't integrate into the cells' DNA, maintaining a presence only long enough to trigger the cell's transformation.

New Cells Induced

Before Yamanaka's breakthroughs, researchers recognized two major types of stem cells. Those derived from days-old embryos are the most powerful, with the ability to generate all of the tissues of the body. Since the process of extracting the stem cells destroys the embryo, their use has stirred ethical debate.

Adult stem cells, found in the organs of developed people or animals, have a more limited ability to form new cells, usually those in that same organ.

Yamanaka's previous work creating what he call induced pluripotent stem cells, or IPS cells, blurred the lines between the two cell types, allowing researchers to change adult cells into the functional equivalent of embryonic cells.

Efficiency Needed

The newest method for creating IPS cells is inefficient, with fewer than 30 colonies of induced stem cells emerging from 10 million mouse cells that were inserted with the gene-bearing plasmids. The efficiency will need to improve, and researchers will have to perform the same feat with human cells, for it to be a viable way to deliver cells as therapy, said Jeanne Loring, director of the Center for Regenerative Medicine at Scripps Institute in La Jolla, California.

While Yamanaka's newest method ``is currently a very tedious and inefficient procedure, it's a good waypoint in the path toward a clinically acceptable method for reprogramming cells,'' Loring said in an Oct. 7 e-mail.

To develop the new technique, Yamanaka and his colleagues used trial and error. First, they used viruses to deliver three genes into mouse cells, noting the sequence that worked best to turn them into IPS cells. Then they loaded the genes into two different plasmids and alternated inserting the plasmids into the cells over four days.

Cells Coaxed

While this approach successfully created IPS cells, Yamanaka and his colleagues found that the plasmids did lodge in the DNA of the cells, an unwelcome result. So they modified their technique and tried different sequences of delivering the plasmids and the genes, also called transcription factors, to the cells.

``By giving the cells a dose of DNA containing transcription factors every other day for a week, they managed to coax a few cells into becoming pluripotent, without any trace of the foreign DNA remaining,'' Loring said.

Yamanaka is now working to create human IPS cells using this process, said Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease in San Francisco, in an Oct. 6 e-mail. Srivastava works closely with Yamanaka, who maintains a research lab at the institute and spends several days a month there.

Hurdles remain before Yamanaka's procedure can be used to make cell therapies for people, Srivastava said, ``but the pace is moving fast.''

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.

Last Updated: October 9, 2008 14:00 EDT