乌鸦传媒

TORONTO, March 3 -- In what is being hailed as a major advance, researchers here and in Great Britain have found a way to make stem cells from skin with fewer risks to potential patients.

The method, reported in two companion papers in Nature, eliminates the need to use a virus in reprogramming the skin cells to become so-called "induced pluripotent stem cells."

Skin cells have previously served as a source of such pluripotent cells, which have the potential to become a vast range of tissues, but the method carried the risk of disease. (See: Adult Skin Cells Reprogrammed into Stem Cells for Disease Research)

In the earlier experiments, a virus was used to carry four genes into skin cells. The genes reprogrammed the skin cells to act as stem cells, but the virus itself was considered a potential danger, since it could disrupt the DNA of a patient's cell and possibly cause cancer.

In the Nature papers, researchers reported two tricks that, in combination, avoid the risk.

In Toronto, Andras Nagy, Ph.D., of Mount Sinai Hospital, and colleagues developed a method -- dubbed "piggyBac" -- to carry the four genes (c-Myc, Klf4, Oct4, and Sox) into the target cell.

The method involves a transposon -- a mobile piece of DNA often referred to as a "jumping gene" -- which can insert the four genes. Each individual gene can then be removed, but it is difficult to ensure that all four are taken out.

A group led by Keisuke Kaji, Ph.D., of the MRC Centre for Regenerative Medicine at the University of Edinburgh, and colleagues, solved that problem.

Dr. Kaji and colleagues had developed a single construct that included the coding regions of all four genes. When the construct was delivered by the piggyBac system, it could easily be removed, leaving little or no trace of the genetic manipulation.

The four-gene construct, however, had the same effect on the target cells as the genes inserted as separate units.

The two groups collaborated closely and shared several members.

Much of the work was performed in mice, where the reprogrammed cells were injected into blastocysts and shown to produce a range of tissues in the resulting embryos.

However, the researchers also used the method to reprogram human embryonic fibroblasts into cells that carried the characteristic marker genes seen in pluripotent cells.

"Using our method, it will be possible to remove not only the inserted genes, but all traces of our genetic modification from the human (pluripotent) cells, although we still need to improve the efficiency," Dr. Nagy said in a statement.

"We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable," he added.

The two studies did not completely demonstrate that the method works in human cells, according to Robin Lovell-Badge, Ph.D., of the United Kingdom's MRC National Institute For Medical Research.

"The tests applied in these two papers fell short of proof that they had obtained truly pluripotent human cells," he said in a statement. "For example, they could have performed a far more extensive battery of molecular tests."

On the other hand, he added, "I see no reason why the new methods should not work."

"I would consider these two papers to be exciting steps in the right direction, but we must not forget that the path is still very long and winding and full of bear traps," Dr. Lovell-Badge said.

In particular, he said, the availability of stem cells derived using this method won't completely eliminate the need for human embryonic stem cells -- a flashpoint for opposition to stem cell research.

Other researchers said that the potential of the work is great.

The cells "can certainly be exploited therapeutically and will be useful for research purposes," said Michael Rudnicki, Ph.D., of the University of Ottawa, who was not involved in the study.

The research is a "great advance," he told reporters.