Local firm details stem cell advance

By: Bradley J. Fikes - Staff writer | Sunday, August 19, 2007 11:18 PM PDT ∞

OCEANSIDE ---- A local biotechnology start-up says it has crossed a major hurdle in embryonic stem cells research by growing the cells directly from unfertilized human eggs.

If confirmed, the advance could lead to a host of medical advances and at the same time defuse a bitter debate on the ethics of this controversial technology.

Because the egg cells were never fertilized, there was no conception and thus no embryo, according to Jeff Krstich, president and chief executive of International Stem Cell Corp. Critics have opposed use of embryonic stems cells, arguing that such research destroys human life.

However, research with the Oceanside-based company's stem cells should meet President Bush's requirements for federal funding, Krstich said. The president has banned the use of federal money for research on stem cells created after August of 2001.



Getting around it

Evan Snyder, an influential stem cell researcher familiar with Bush's restrictions, agrees with Krstich.

"I think it would circumvent the ban," said Snyder, who heads the stem cell research program at the Burnham Institute in La Jolla. That would open the door to funding from the National Institutes of Health, the nation's single biggest funder of medical research. But proving that the Oceanside company's cells work is the big challenge, he said.

Embryonic stem cells are the "ancestral" cells that turn into the hundreds of cell types in the human body. They are normally taken from days-old human embryos made by normal fertilization with sperm or by cloning, a technique that creates a genetic duplicate of an organism.



'Remains to be seen'

To be used in therapy, stem cells must be transformed, or differentiated, into the needed cell type, then transplanted into the patient.

"I just think it remains to be seen how normal they would behave when differentiated, and most importantly when transplanted," Snyder said.

Even if this "parthenogenetic" method works, however, some influential organizations, including the Catholic Church, have indicated they would oppose this method as well.

Researchers around the world are investigating whether embryonic stem cells can be used to treat diseases and injuries, such as paralysis from spinal cord damage. Krstich said his company's parthenogenetic cells could be used to treat people with diabetes, eye and liver disease by as early as next year.



Booster potential

If the company is successful, it will greatly boost San Diego County's visibility as a center of stem cell research. Local companies such as Carlsbad's Invitrogen Corp. and research centers including UC San Diego and the Burnham Institute in La Jolla, have made stem cell research a major priority. Krstich said he relocated the company from Los Angeles to Oceanside a year ago in order to tap into the area's biotech expertise.

Lending validity to the claim, the company has published a scientific paper describing its results. The paper appeared in the June 26 issue of Cloning and Stem Cells Journal. The journal is edited by Ian Wilmut, the Scottish scientist whose team created Dolly, the first cloned mammal.

The paper said embryonic stem cells were derived six times from unfertilized eggs, creating six "lines" of these stem cells. (Since then, Krstich said, the company has created six more embryonic stem cell lines).

"This is the first time to my knowledge that it's been in print," said Larry Goldstein, director of UCSD's stem cell research program. "It's been done in other primates, but not in humans."



Hope for transplants

Because they're produced from unfertilized eggs, the company's stem cells closely resemble the genetic makeup of the donor women, Krstich said. This means it should be easier to create replacement tissue for transplants that is not rejected by the recipients.

The cells produced by the company's scientists are "pluripotent," which can turn into nearly all of the cell types, according to the paper.

In animal studies, the stem cells have been used to make paralyzed rats walk. The cells were transformed into neural tissue and transplanted into the paralyzed rats. The tissue repaired the rats' damaged spinal cords, according to research by Hans Keirstead, a stem cell researcher at UC Irvine.

Krstich said the company has produced insulin-producing "islet" cells, retinal cells and liver tissue from the embryonic stem cells, and that animal studies will soon be under way. The company has teamed up with Keirstead for studies on treating retinal disease.



Is it legal?

Many scientists believe the embryonic stem cells have a potential for therapies superior to so-called "adult" stem cells, taken from adults or umbilical cord blood. That is because the embryonic stem cells retain more of their ability to turn into different cell types. Adult stem cells have partially transformed into mature cell types.

International Stem Cell thinks its workaround is also more effective in making stem cells than other methods.

"We take the egg, we chemically treat it ---- that's our patented process ---- it grows to a group of cells called a blastocyst," Krstich said. "We extract the stem cell, and from there, we take the stem cell and we expand it or grow it to a certain size, and then we freeze it. When we thaw it out, we can continue to expand it."

Krstich said this method produces one line of embryonic stem cells from every two egg cells, a far higher proportion than in previous methods. Moreover, he said, it doesn't violate Bush's funding restrictions.

Opponents say that regardless of whether embryonic stem cells turn out to be better therapy, getting them violates the right to life of embryos as human individuals, because the embryos are destroyed to get the cells.

In 2001, President Bush cited that moral concern in restricting federal funding of human embryonic stem cell research to stem cell lines created by August of that year. Previously, no such research had received federal funding.



Congress involved

However, a spokesman for the National Institutes of Health, the largest funder of biomedical research, said International Stem Cell's research would fall afoul of a federal law called the "Dickey-Wicker Amendment." The amendment has been added by Congress each year since 1995 to the bill that funds NIH, said the spokesman, Don Ralbovsky.

The amendment defines a human embryo as, "any organism, not protected as a human subject . . . that is derived by fertilization, parthenogenesis, cloning or any other means from one or more human gametes or human diploid cells."

In 1999, Harriet Rabb, then general counsel of the Department of Health and Human Services, issued a legal opinion that the restriction only applied to funding the process of extracting embryonic stem cells from embryos, not the subsequent use of the embryonic stem cell lines.

However, the Bush administration reversed that opinion, and with Bush's decision to restrict funding on his own, the amendment became a non-issue. That could change if the next president decided to end the funding restrictions.



Moral questions

The morality of embryonic stem cell research revolves around what makes a human being.

Krstich said his company's cells don't have the potential to become human beings and so aren't real embryos.

"For most people, we do not think we violate their ethical standards," he said. "Most scientists agree, you cannot create a human being with an egg. You need the egg and the sperm. We only use the egg."

Art Caplan, a bioethics expert at the University of Pennsylvania, isn't so sure that will quell the controversy.

"Some will say if that thing looks like an embryo, acts like an embryo, is being treated as an embryo, then it is an embryo," said Caplan, who is also on the editorial board of the scientific journal that published the company's research.



Catholics agree

The National Catholic Bioethics Center, which reflects official Catholic teaching, takes this position.

"Because Dolly the Sheep was made without sperm, this does not imply that she was some kind of being other than a sheep. Similarly, a human embryo made without sperm is not some kind of being other than a human," the center stated on its Web site at: http://www.ncbcenter.org/10Myths.pdf.

The company's small scale helps it conserve money, Krstich said. Isolating and culturing embryonic stem cells is not labor-intensive work. It has 15 employees, about seven of those in Oceanside and eight in a subsidiary, Lifeline Cell Technology, in Walkersville, Md. That subsidiary occupies about 4,000 square feet, while the Oceanside headquarters occupies 8,000 square feet.

By the end of the year, about 20 employees will be working in Oceanside, Krstich said.

In addition, the company is raising money from performing biological work for other companies. Krstich said this reduces the money the company needs to raise from investors.

However, being small also works against the publicly traded company, which is not well-known.

Shares of International Stem Cell went for $1.00 apiece on Friday, giving it a total stock value of about $40 million. That's minuscule by the standards of public companies The company's stock is traded over the counter under the symbol ISCO.OB.

Stories about the production of embryonic stem cells tended to focus on the company's subsidiary. A June 28 Associated Press article failed to mention the parent company.

Contact staff writer Bradley J. Fikes at (760) 739-6641 or bfikes@nctimes.com. Comment at nctimes.com.

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