Harvard Scientists Report a Stem Cell Advance

Scientists at Harvard say they have developed a technique that offers a long-range possibility for producing therapeutic stem cells without a need to harvest them from discarded human embryos.

The technique, which involves fusing two cells together, sheds light on how an adult cell like a skin cell can be reprogrammed back to its embryonic state. Scientists hope that cells in this state can be developed into the tissue needed for repairing a damaged brain or heart or other ailing organ.

The technique is described in an article by Kevin Eggan, Chad A. Cowan and other Harvard biologists, to appear Friday in Science. The journal released the paper early because its results had been described at a scientific conference. They were reported yesterday in The Washington Post.

Any recipe that avoided the use of embryos might be welcomed by opponents of stem cell research. But the Harvard article may have little political impact, since it could be many years, if ever, before the technique becomes applicable to humans.

The idea of such regenerative medicine is to generate embryonic cells from a patient and develop them into the specialized cells that can replace those lost to disease. The only practical method at present, to judge from experiments with mice, is to take the nucleus of a patient's skin cell and insert it into an unfertilized human egg whose own nucleus has been removed; unknown factors in the main body, or cytoplasm, of the egg make the chromosomes of the introduced nucleus revert to an embryonic state. This reprogramming is apparently executed by switching off banks of genes used by the specialized adult cell, and switching on other genes that restore the cell to its full youthful potential.

Scientists have long tried to identify these mysterious reprogramming factors, because once known they could be injected directly into one of the patient's skin cells to make it embryonic, without the difficulties of nuclear transfer into human eggs.

In the Harvard study, the researchers have fused an embryonic stem cell with a human adult cell, and shown that the stem cell, like the unfertilized egg, can reprogram the adult cell's chromosomes. They hope the combined cell will provide another system in which to hunt for the elusive reprogramming factors, which could be synthesized and used to redirect a patient's cells.

So complete is the embryonic cell's takeover that the fused cell behaves just like one. This raises a second possible therapeutic approach: that of using the fused cells themselves to make replacement tissues. Such an approach would require continuing the use of stem cells from embryos, though existing lines of them might be sufficient for the task.

In this approach, the fused cells, being half-foreign to the patient, would be rejected, and in any case the combined cell, with twice the proper number of chromosomes, could probably not survive. Still, the approach could be effective if the embryonic stem cell's chromosomes could somehow be removed from the combined cell just after they had executed their reprogramming maneuver.

"I think physical biologists will work out a way of doing that" over the long term, said John Gearhart, a stem cell biologist at Johns Hopkins University who was not involved in the Harvard research.

In the egg, it is factors in the cytoplasm that reprogram the introduced nucleus. In embryonic stem cells, however, it has turned out to be the chromosomes in the nucleus that possess the reprogramming power, Dr. Gearhart said, because the cells lose that ability once their nucleus is removed.

Once the two nuclei of the combined cell fuse together, it is virtually impossible to disentangle their chromosomes. But there might be a short interval, after the membranes surrounding each nucleus have dissolved, when the embryonic cell's chromosomes could somehow be evicted from the cell, Dr. Gearhart said. Such a cell would contain only the patient's genes and would be excellent source material for a therapeutic patch.

Other long-term alternatives to the present therapeutic approach involving stem cells were advocated earlier this year by President Bush's Council on Bioethics. Dr. Gearhart said that those approaches should be pursued but that since all were at least 5 to 10 years away, they should not be allowed to impede development of the current approach. The Harvard report adds a new way of pursuing the reprogramming factors and puts cell fusion on the table as another alternative technique.