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Harvard researchers, Advanced Cell Technology publish new method of turning skin cells into stem cells
06-08-2009
by David Hutton  |  Email the author
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WORCESTER, Mass.—A team at Harvard University and Massachusetts-based Advanced Cell Technology Inc. have taken another step forward in the development of technology for versatile, grow-in-a-dish transplant tissue, announcing that they have found a safe way to turn skin cells into stem cells.

According to the research team, their technique involves soaking cells in human proteins that turn back the clock biologically, making the cells behave like powerful embryonic stem cells.

"After a few more flight tests—in order to assure everything is working properly—it should be ready for commercial use," study co-author Dr. Robert Lanza of Advanced Cell Technology told Reuters. He added that the initiative would ask the U.S. Food and Drug Administration (FDA) to allow the beginning of human clinical trials by as early as next year, although chances of that happening are fairly slim.

The study was recently published in the online edition of Cell Stem Cell.

Lanza also pointed out that the discovery might be the first safe method of generating patient-specific stem cells.

In recent years, several teams of scientists have focuses on four genes that can turn back the clock in ordinary cells, making them look and act like embryonic stem cells. The result is induced pluripotent stem cells, or iPS cells, that could in theory be made using a patient's own skin, allowing grow-your-own transplants with no risk of rejection.

"This technology will soon allow us to expand the range of possible stem cell therapies for the entire human body," Lanza said in a statement. "This allows us to generate the raw material to solve the problem of rejection (by the immune system) so this is really going to accelerate the field of regenerative medicine."

Of course, getting the genes into cells isn't easy work. Initial efforts used retroviruses, which integrate their own genetic material into the cells they infect. Other attempts used loops of genetic material called plasmids or other genetically engineered molecules to reformat the cells.

And another team used the proteins made by the four genes and valproic acid to reprogram cells, but Lanza said these methods all have drawbacks.

His team, working with Kwang-Soo Kim of the Harvard Stem Cell Institute and a team at CHA Stem Cell Institute in South Korea used a peptide, a protein fragment, to drag the human proteins into the cells.

"These have been around for a long time," Lanza said. "The AIDS virus uses the peptide to get into the cells it infects."

The work of Lanza's team is drawing praise from peers.

A research scientist at Kansas State University told Kansas Liberty that the results of the team's research could hasten a movement away from controversial embryonic stem cell research.

Dr. Masaaki Tamura, associate professor of anatomy and physiology at Kansas State University and himself a stem cell researcher, said the announcement by Lanza was a "big breakthrough."

Tamura noted that the development could point science toward the day—perhaps sooner rather than later—when stem cells derived from the skin and suitable for treating all kinds of human diseases and conditions could be reaped from "a swab of the mouth or a scraping of the skin," rather than through the destruction of a human embryo.

Tamura said, in effect, the process reverted specialized adult cells into more "primitive" and pluripotent embryonic-stem-cell types.

"It was like evolution in reverse," he told Kansas Liberty.

The method developed by Lanza's team differs from a technique unveiled three years ago at Kyoto University that deploys viruses to deliver genes into cells and reprogram them.

Lanza said the new method eliminates risks associated with genetic and chemical manipulation. It also provides a way for patients to contribute cells that would be combined with proteins, grown into stem cells and used to generate other cells for the patient's treatment.

"Not only can you create these stem cells, but they're your own stem cells, so you don't have to worry about rejection," Lanza told the Worcester Telegram.

At Kyoto University, Shinya Yamanaka and his team introduced four genes into skin cells, reprogramming them so that they became indistinguishable from embryonic stem cells.

The achievement by the Kyoto group conjured the distant vision of an almost limitless source of transplant material that would be free of controversy, as it would entail no cells derived from embryos.

It did come with a downside, being that the technique for creating the induced pluripotent stem cells is that the genes are delivered by a "Trojan horse" virus.

Reprogramming cells using a virus modifies their DNA in such a way that they cannot be given to patients without boosting the risk of cancer and genetic mutation.

Other researchers have succeeded in delivering the genes with a method called DNA transfection or using a chemical wash, but these techniques also posed health risks.

Lanza's team succeeded in delivering the genes by fusing them with a cell penetrating peptide which does not pose the risk of genetic mutation.

While this method took twice as long to generate pluripotent stem cells, Lanza said he believes his team can increase the efficiency of the transmission by purifying the protein.

Promoters say this material could reverse cancer, diabetes, Alzheimer's and other diseases and also allow researchers to grow patient-specific organ and tissue transplants that will not require harmful anti-rejection drugs.

But the dynamic has been sapped by opposition from religious conservatives, who argue that research on embryos—the prime source of stem cells so far—destroys human life.

Generating stem cells from skin cells bypasses the controversy and also dramatically increases the availability of patient-specific stem cells.

Advanced Cell Technology did not respond to interview requests.

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