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S.D. firm's work major step toward creating stem cell lines
By Terri Somers
UNION-TRIBUNE STAFF WRITER

January 17, 2008

Video of thhttp://www.signonsandiego.com/news/business/biotech/20080117-9999-1n17embryo.htmle somatic cell nuclear transfer process used by San Diego-based Stemagen.

A team at the tiny San Diego biotechnology company Stemagen has become the first to document its successful cloning of human embryos by fusing donated egg cells with the DNA from skin cells of an adult man, according to an article that will be published online today by the journal Stem Cells.
The company's work, led by chief science officer Andrew French, is a major step toward creating embryonic stem cell lines from cloned human embryos, or cells that are specific to one person and capable of evolving into the 200 different cell types in the body.

Theoretically such cells one day could be used as a human toolbox: Someone's own embryonic stem cells could be transplanted into that person without the fear of rejection and could replace cells destroyed by diseases such as diabetes and Parkinson's.

The process, known as therapeutic cloning, has plenty of opponents because the embryo theoretically could be implanted into a woman's uterus for reproduction.

As human cloning advances, ethics debate gets louder


Reproductive cloning is illegal in California, and Stemagen said it stuck to a research protocol that met all current medical and ethical standards.

The company's team was giddy with the excitement of finally sharing their accomplishment.

“No other scientific group has documented the cloning of an adult human cell, much less been able to grow it to the blastocyst stage . . . the stage that yields the cells from which embryonic stem cell lines are made,” French said.



CHARLIE NEUMAN / Union-Tribune
Stemagen's Andrew French on the work he led: "No other scientific group has documented the cloning of an adult human cell."
However, others have claimed such a feat. In February 2004, a South Korean scientist claimed to have cloned human embryos through the same process, known technically as somatic cell nuclear transfer, or SCNT. The Korean work was exposed as fraudulent the following year, casting a pall upon the scientist and, some thought, the entire field.

In the ensuing years, several scientists have cloned animal embryos using the process. In November, a team from Oregon National Primate Research Center reported successfully cloning embryos from monkeys, a step that scientists thought moved the process closer to working in humans.

Meanwhile, scientists at Harvard, the University of California San Francisco and UC Irvine have said they are trying to create human embryonic stem cell lines through SCNT. None of those scientists could be reached to comment on Stemagen's work.

Stemagen CEO Samuel Wood said the privately held company accomplished the feat in humans in May 2007. Because of the South Korean controversy, the company did not want to reveal its success until the work could be verified through genetic testing and then published in a peer-reviewed journal, Wood said.

And that took months.

“We wanted to rekindle interest in this area with a very detailed article describing exactly how to do it,” Wood said.

Meanwhile, other scientific teams published journal articles that had scientists and patient activists buzzing.



Stemagen
The first indication that the cloning of an embryo has been successful is the observation of a pronucleus (above) that contains material from the donor skin cell.
Scientists from Japan and the University of Wisconsin said in November that they could genetically and chemically coax human skin cells to move backward down the development pathway until they reverted to pluripotent cells, which have the ability to become many different cell types in the body.

Just last week, California-based Advanced Cell Technology showed that it had grown embryonic stem cell lines by removing one cell from an eight-cell embryo and coaxing it to develop.

That work may have eclipsed Stemagen's somewhat in the eyes of scientists. Jeanne Loring of the Scripps Research Institute in La Jolla said it's not the huge event it would have been before some of the other recent advances.

Loring applauded the work.

“This is a great milestone,” said Loring, who heads the institute's human embryonic stem cell research program. “It's important because it sort of wipes away the blot on science left by the Korean scandal by showing this really can be done.”

Officials at the California Institute for Regenerative Medicine, which is pouring $3 billion into stem cell research over the next decade, were excited about the company's work and the avenues it paves.

“It's great to see them make progress in SCNT in human cells,” said Richard Murphy, outgoing president of the stem cell institute. “We want progress to be made in all areas of research, and this finding expands the potential for success in therapeutic approaches.”



Other embryonic stem cell scientists agreed with the institute's take.
Larry Goldstein, a Howard Hughes investigator at UC San Diego, said he wants “the biggest toolbox he can get.” That would include stem cells created by SCNT and stem cells created by the reprogramming approach demonstrated in Wisconsin and by Japanese scientists, Goldstein said.

Genes and viruses used to reprogram the cells have been linked to diseases such as cancer. For reprogrammed cells to be used in humans, scientists still must figure out a way to coax them to revert to pluripotency with proteins or chemicals that will not cause disease, Goldstein said.

Also significant in Stemagen's work, scientists said, is that it used 25 donated human eggs to create five human blastocysts, of which three were confirmed genetic clones.

Using as few eggs as possible is important because California law dictates that donors can't be paid, which makes it difficult to obtain eggs.

Stemagen ultimately hopes to sell stem cell lines from people with diseases to drug companies, which could use them to test the effects of new drugs, Wood said. It also plans to create cell lines for people who want them available should they need them for a therapy, he said.

Stemagen believes its access to eggs from young donors who already have donated eggs used in successful in-vitro fertilization is crucial to its success.

Wood runs the Reproductive Sciences Center in La Jolla, the in-vitro fertilization clinic that obtains the eggs. After a woman donates several for in-vitro fertilization, there are often several left over. It is the leftover eggs that are donated to Stemagen.

Another key to success, French said, is that the SCNT process begins on the eggs within the hour after they are extracted. Previously documented unsuccessful SCNT procedures began the process hours later, and sometimes used eggs that were not viable for reproduction, he said.

The process starts by removing the egg's genetic material and fusing it with skin cells from Wood or another man. Soon, the genetic material in the skin cell takes control as the egg develops into the early stage embryo, French said.

The company chose to stop there and verify it had a cloned embryo rather than attempt to derive embryonic stem cells from them. Deriving embryonic stem cells and creating a line of them is very tricky and could fail, while destroying the embryo, Wood said.

Meanwhile, genetic testing of the embryos confirmed that they contained the DNA of only the male skin cell donor, and were therefore clones.

During the past several months, the company has been perfecting its process for creating embryonic stem cell lines, and using that process to try to derive stem cells from cloned blastocysts, he said.

"Developing patient-specific stem cell lines from these blastocysts is the holy grail,” Wood said. “We know this report stops short, but it shows the entrance to the cave holding the holy grail.”

Union-Tribune library researcher Denise Davidson contributed to this report.


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Terri Somers: (619) 293-2028; terri.somers@uniontrib.com