Thursday, 6 October 2011

Cloning Offers Stem-Cell Hope

Researchers said Wednesday they used a cloning technique to create human embryos that were close genetic copies of the people from which they were derived—a potentially significant breakthrough in the quest to develop patient-specific stem cells to treat serious diseases.
Scientists involved in the experiment, which was published in the journal Nature, created 13 early-stage human embryos that were partial genetic clones of diabetic patients. The copies were not identical, as each embryo carried three sets of chromosomes—an extra set. That means they were abnormal and wouldn't have been viable if implanted in a womb and carried to term.
If the technique is ever to become a viable treatment, the researchers would have to eliminate the extra set of chromosomes and effectively create an embryonic human clone.
Nevertheless, the experiment marks the closest scientists have come to cloning humans as a route to developing medical treatments. In 2004, a South Korean scientist claimed to have created the first human embryonic clone and derived a stem-cell line from it, but that work was shown to be fraudulent. While the latest study doesn't claim the same dramatic breakthrough the 2004 experiment did, it is likely to spark controversy because it involves potential human cloning and embryo destruction.
"It's an early research step… towards curing devastating diseases," said Dieter Egli of the New York Stem Cell Foundation Laboratory in New York City and a co-author of the study, which pointedly doesn't use the word "cloning" to describe the results. "We really don't know how hard it's going to be" to eliminate the extra chromosomes, he said.
Scientists have long hoped to create fresh human tissue and use transplantation to treat a range of ailments, such as heart disease and Parkinson's. Ideally, such fresh tissue should share the same DNA as the patient and thus avoid immune-rejection problems.
There are several ways to create fresh tissue. Master stem cells—which give rise to all tissue types in the body—can be extracted from a 100-cell embryo, or blastocyst. But this approach is ethically controversial and doesn't get around the problem of immune rejection.
Alternatively, certain genes can be added to a patient's mature cells. This reprograms them into an embryo-like state and creates a source of master cells without the problem of immune rejection or ethical controversy. But this method is still a long way from being safe or useful.
A third way is to use eggs to do the reprogramming trick. That was how Dolly, the famously cloned sheep, was made: her mother's skin cell was put in another sheep's egg, which no longer had its own DNA-containing nucleus. That effectively "rebooted" the skin cell into an embryonic form, which was carried to term and led to a cloned Dolly.
While such cloning experiments have been successful in various mammals, the "de-nucleated" egg approach hasn't worked so far in humans. Now, Dr. Egli and his colleagues have—partially—achieved it via a simple move: They didn't remove the egg's own nucleus.
As a first step, they took the DNA-carrying nuclei from skin cells of diabetic patients and added them to unfertilized human eggs. The eggs reprogrammed the added cells, creating blastocysts, which are 100-cell embryos, each tinier than a pin-head. The researchers then derived stem-cell lines from the blastocysts, a move that destroys the blastocyst.
The ultimate goal would be to transform the stem cells into insulin-producing cells and put them back into the diabetic patients without fear of immune rejection. The scientists didn't go that far, since they knew the created embryos had an extra set of chromosomes—originating from the egg—and were thus abnormal.
Nonetheless, the eggs did successfully reprogram the patients' skin cells into master stem cells. As a test, the team successfully converted those master stem cells into various other cell types, including nerve, cartilage and muscle tissue.
"I think this paper is a landmark, even though it isn't a complete victory," said George Daley, a stem-cell researcher at Children's Hospital Boston, who read the paper but wasn't involved in the study. "It's proof of principle that [the cloning technique] can successfully reprogram" mature human cells.
The technique is inefficient, however, Dr. Egli and his colleagues said they started with 270 eggs and created 13 early-stage embryos. From these, they obtained only two viable stem-cell lines.
The method also relies on human eggs, which can be hard to obtain for research purposes. In this case, 16 women donated the 270 eggs. They were compensated.
Dr. Daley believes the difficulty of obtaining human eggs is one reason why the other reprogramming approach—using genes—may be more feasible in the long run.
A key technical problem is ridding the stem cells of the extra set of chromosomes. The team hopes that by experimenting with some other starter cell—not skin—they might get a better result. "For the first time we have an experiment that actually works, so we can optimize from there," said Dr. Egli.

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