Monday, July 27, 2009

Chinese Scientists Reprogram Cells to Create Mice

http://online.wsj.com/article/SB124839803784477915.html

By GAUTAM NAIK

Two teams of Chinese researchers working separately have reprogrammed mature skin cells of mice to an embryonic-like state and used the resulting cells to create live mouse offspring.

View Full Image
A picture released by Nature magazine shows Xiao Xiao, or Tiny in Chinese, the first baby mouse created from reprogrammed skin cells.
Agence France-Presse/Getty Images

The reprogramming may bring scientists one step closer to creating medically useful stem-cell lines for treating human disease without having to resort to controversial laboratory techniques. However, the advance poses fresh ethical challenges because the results could make it easier to create human clones and babies with specific genetic traits.

The latest findings are a bit of a surprise, given that Chinese scientists' contribution to lab-based stem-cell research has been modest over the years. However, Chinese scientists have been publishing more basic-research findings than in the past. The country is more known for its growing trade in unproven stem-cell therapies that have attracted patients from around the world. Reports suggest that China's health authorities have moved to regulate such activities.

Reprogramming has become the hottest area of stem-cell science. For more than two years, scientists have been reprogramming mature mouse- and human-skin cells and returning them to a primordial, embryonic-like state. The approach has taken off because it sidesteps the cloning and embryo-destroying techniques traditionally used to derive true embryonic stem-cell lines.

However, one big question has been whether reprogrammed cells are as versatile as true embryonic cells, and whether they can form all of the cells in an embryo. Using reprogrammed cells to create live offspring with normal organs and body tissues has been considered an important test. Chinese scientists now have shown that this is possible in mice.

In their study published in the journal Nature, scientists led by Qi Zhou of the Chinese Academy of Sciences in Beijing described how they injected reprogrammed mouse cells into an early-stage embryo to see whether the introduced cells contributed to the tissue of the eventual fetus. Of 37 stem-cell lines created by reprogramming, three yielded 27 live offspring. One of these pups, a seven-week-old male named "Tiny," mated with a female and produced young of its own.

In a similar experiment, Shaorong Gao and colleagues from the National Institute of Biological Sciences in Beijing got four live births, including one mouse pup that made it to healthy adulthood. Their results were published online in the journal Cell Stem Cell.

The results don't necessarily prove that reprogrammed cells have the same properties as true embryonic stem cells. Scientists previously have injected cells that cannot be converted into other tissue into an early-stage embryo. To their surprise -- and this might reflect the power of any embryo -- even those cells got incorporated into fetal tissue.

Dozens of scientists have now created reprogrammed human cell lines, and the techniques are being constantly refined. What if the same experiment, as reported in China, were carried out in humans? To do so, a skin cell, say, could be reprogrammed to an embryonic-like state, then injected into an early-stage human embryo, obtainable from many fertility clinics.

The result of that experiment will likely be a human chimera -- a person that shares genes from two people but isn't the result of natural reproduction. The more refined such experiments get, the closer they will get to cloning.

In the Nature paper, the scientists reported that some of their offspring mice were as much as 95% genetically identical to the adult mouse whose cells were originally reprogrammed -- very close to an exact clone. For that reason, most scientists won't even try to repeat the Chinese experiments in humans.

But it could be done. "There's no biological reason why, if you inject human reprogrammed cells into a human embryo, it won't create a clone," or at least a chimera, says Robert Lanza, a stem-cell scientist at Advanced Cell Technology Inc. in Worcester, Mass. "All you need are somebody's skin cells to create a human baby." Dr. Lanza predicts this could happen in a place where the rules about creating chimeras and human clones are a lot more lax than in the U.S.

Write to Gautam Naik at gautam.naik@wsj.com