Scientists Report Advance in Stem Cell Alternative

By Rob Stein
Washington Post Staff Writer
Friday, September 26, 2008

Scientists reported yesterday that they have overcome a major obstacle to using a promising alternative to embryonic stem cells, bolstering prospects for bypassing the political and ethical tempest that has embroiled hopes for a new generation of medical treatments.

The researchers said they found a safe way to coax adult cells to regress into an embryonic state, alleviating what had been the most worrisome uncertainty about developing the cells into potential cures.

"We have removed a major roadblock for translating this into a clinical setting," said Konrad Hochedlinger, a Harvard University stem cell researcher whose research was published online yesterday by the journal Science. "I think it's an important advance."

The development is the latest in the rapidly advancing and politically charged field of stem cell research.

"This is a huge step forward -- it could be the breakthrough we've been looking for," said Robert Lanza, a stem cell researcher at Advanced Cell Technology in Worcester, Mass.

Embryonic stem cells are believed capable of becoming any type of cell in the body. Researchers hope to eventually use them to create replacement tissue and body parts tailored to individual patients. But the work has run into moral objections because the cells were originally obtained by destroying early-stage embryos. As a result, President Bush has restricted federal funding for such work.

Scientists last year shook up the scientific and political landscape by discovering how to manipulate the genes of adult cells to convert them into the equivalent of embryonic cells -- entities dubbed "induced pluripotent stem cells," or iPS cells -- which could then be transformed into any type of cell in the body. Subsequent work has found that the cells can alleviate symptoms of Parkinson's disease and sickle cell anemia in mice.

But the first iPS cells were created by ferrying four genes into the DNA of adult cells using retroviruses, which can cause cancer in animals. There was also concern because the viruses integrated their genes into the cells' DNA. In the new work, Hochedlinger and his colleagues used a different type of virus, known as an adenovirus, to carry the same four transformative genes into the DNA of mouse skin and liver cells. The adenovirus does not integrate its genes into a cell's DNA and therefore is believed to be harmless.

"The adenovirus will infect the cells but then will clear themselves from the cells. After a few cell divisions there are no traces of the virus in the cell," Hochedlinger said. "You can't tell the virus was ever there."

As with iPS cells produced using retroviruses, tests showed that the new cells were indistinguishable from embryonic stem cells and could be transformed into any type of tissue, including lung, brain, heart and muscle; unlike the retrovirus-engineered cells, they do not produce cancerous tumors.

"What our experiment shows is you can do this without an integrating virus. You do not need integration of the DNA into the genome to produce iPS cells," Hochedlinger said.

Rudolf Jaenisch, a professor of biology at the Whitehead Institute in Cambridge, Mass., praised the work but noted that the process is 100 times less efficient than using retroviruses.

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