A. French et al., Stem Cells (17 January 2008)

Promising growth.
(Clockwise from left) Three-, 5-, and 6-day-old cloned blastocysts.

Human Embryos Cloned From Skin Cells

A California company reported today that it has, for the first time, cloned human embryos using DNA from adult skin cells. That's "an important first step" toward generating embryonic stem (ES) cell lines from such embryos, which can be used to study and treat diseases such as diabetes and Parkinson's, says stem cell researcher George Daley of Harvard Medical School in Boston.

Scientists want to be able to clone early human embryos, using cells from patients with various diseases, so they can study the diseases in the lab and develop new treatments for them. A major breakthrough occurred last year when scientists figured out how to turn skin cells into ES-like cells that could serve the same purpose (Science, 23 November 2007, p. 1224). But they still want to be able to do cloning, otherwise know as somatic cell nuclear transfer (SCNT), because embryonic cells are the "gold standard" for pluripotent cells--cells that can become any cell type in the body. In addition, scientists want to learn more about how an oocyte can reprogram a mature cell back into an ES cell.

In the new study, a research team at Stemagen, a biotech company based in San Diego, California, started with skin cells donated by two men and 25 eggs, or oocytes, donated by women at a nearby fertility center. The scientists removed the DNA-containing nuclei from the eggs and replaced them with DNA from the donor skin cells. Two of the eggs became 5-day-old embryos, or blastocysts, that were clones of the male donors. That's an "unexpectedly high" success rate, the company said in a statement.

Study leader Andrew French says the key to the team's success was utilizing fresh, mature oocytes from females of proven fertility. "We wanted to access the best raw material," he says. The researchers have also worked with "fail-to-fertilize" eggs discarded from fertility clinics, French says, but these "don't develop--they basically fall apart eventually."

The advance, published online today in the journal Stem Cells, comes less than 2 months after researchers succeeded in generating ES cells from cloned monkey blastocysts--the first time this has been achieved with primates. Both papers mark something of a comeback for the field, which was shaken 2 years ago by revelations about fraudulent research by Korean scientist Woo Suk Hwang (ScienceNOW, 30 October 2006). Mindful of suspicions remaining from the Hwang disaster, the group sent their blastocysts to a separate company to verify the genetic composition. DNA fingerprinting confirmed that two of the blastocysts had the DNA of the male donor cells. In another test, researchers verified that a third had the mitochondrial DNA but no nuclear DNA from the oocyte, indicating that that, too, was a clone. For technical reasons, the genetic makeup of the remaining two couldn't be verified, although the company believes that they are also clones.

Although scientists have welcomed the development, they say the real breakthrough will be when someone manages to extract ES cells from the inner cell mass of cloned blastocysts and generate a cell line from them. That's the only way to get ES cells with the genetic signatures of patients whose diseases they want to study.

Stemagen's team says that's next, but Robert Lanza of Advanced Cell Technology in Worcester, Massachusetts, doubts the researchers could do it with the embryos they have created so far. "There is a large body of data ... showing that [SCNT] leads to chromosomal abnormalities," he says. The blastocysts in the paper "look very unhealthy," says Lanza. "I would guess these clones are abnormal, too." French counters that the director of the clinic that provided the eggs "says she has got pregnancies from IVF [in vitro fertilization] embryos that look similar."

Meanwhile, another advance on the cloning front occurred yesterday in the United Kingdom, where two research teams have at long last gained permission from the government to culture "hybrid" embryos from injecting human DNA into cow or rabbit eggs. The researchers want to use these to study reprogramming without resorting to using hard-to-get human eggs (ScienceNOW, 5 September 2007).

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