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Stem cell breakthrough
21 NOV 2007

Discovery leaps legal, financial and ethical hurdles facing stem cells
This week, two groups of researchers report a technique for making embryonic stem cells without using (or destroying) embryos.

Embryonic stem (ES) cells, do-it-all cells that can form any body tissue, have vast potential for regenerative medicine and disease research. Until now, human ES cells were taken from embryos, causing a welter of financial and legal restrictions on research in the United States.

Woman sits at microscope in clean, well-lighted labOne of today's reports came from Shinya Yamanaka of Kyoto University, who last year "reprogrammed" mouse skin cells to form mouse ES cells, and has now done the same thing with human cells. The second report came from James Thomson, a professor of anatomy at the University of Wisconsin School of Medicine and Public Health.

Junying Yu, lead author of a paper describing a new way to reprogram adult stem cells to create embryonic stem cells, at the microscope. Photo Bryce Richter, University of Wisconsin-Madison.

Thomson said the new technique could sidestep most of the barriers that have slowed stem-cell research. "The induced cells do all the things embryonic stem cells do. It's going to completely change the field."

In 1998, Thomson was the first to grow human embryonic stem cells in the laboratory, an advance that immediately raised the prospect of replacing diseased body tissues with lab-grown spare parts. That approach was particularly suited to diseases caused by the death of small, distinct cell populations, such as type 1 diabetes or Parkinson's disease.

But complications quickly arose, and regenerative medicine with ES cells remains a hope rather than a reality:

Controlling cell development is a subtle, tricky process dominated by complex, little-known biological molecules.

Large numbers of difficult-to-obtain human egg cells were required for ES cell research.

The right-to-life movement vehemently opposed research on embryonic stem cells, condemning as murder the destruction of human embryos that was needed to provide the ES cells. In 2001, federal funding in the United States was restricted to a few strains of embryonic stem cells. Labs and equipment funded with federal money cannot be used to work on any other embryonic stem cells.

By subtracting eggs and embryos from the equation, however, the new technique could produce embryonic stem cells while leaping each of these hurdles.

How done it?
The advances at the Japanese and American labs reflects a better understanding of how genes control development. Both sets of researchers started with fibroblasts -- common cells that create connective tissue in skin and elsewhere -- and introduced four genes that are active in ES cells, but not in adult cells.

As the cells grew in the lab, it was obvious that chemicals made by the introduced genes had reversed the normal course of development. In nature, generalist ES cells make specialized cells, including fibroblasts. The new genes added a step to the natural sequence: Fibroblasts were making embryonic stem cells, which then were making specialized cells.

Colonies of the "induced" stem cells bore all the hallmarks of human embryonic stem cells. For example, some grew in the Thomson lab for 22 weeks without changing into specialized cells.

Stem cells are prone to differentiate, and when allowed to do so, they formed all three basic types of cell. In every test, they looked just like ES cells, Thomson and Yamanaka both reported.

Colony looks like a ball of yarn against background of stray cells
Junying Yu and James Thomson introduced four genes into human skin cells, which are easy to grow in culture, and they apparently were converted into embryonic stem cells. The big glob at center is a colony of embryonic stem cells. Courtesy Junying Yu, University of Wisconsin-Madison.

Sidestepping trouble
The finds reported this week represent a major advance in the field of ES cell research. In 1998, human embryonic stem cells burst upon the scientific scene with all the subtlety of a bulldozer. Since embryonic stem cells could form any cell in the human body, they had obvious potential for regenerative medicine -- for replacing spent or diseased cells with fresh new ones.

The new discovery sidesteps all of the legal and ethical problems associated with ES cells, and it may hasten the day when a patient could supply a few skin cells, and have them transformed -- abracadabra! -- into countless numbers of replacement body cells.

Because a patient would supply the initial cells for transformation, the new method makes stem cells that are native tissue, and thus "are probably more clinically relevant than embryonic stem cells," Thomson explains. "Immune rejection should not be a problem using these cells."

The technique "allows many labs around the world to work on these cells," added Thomson's co-author, Junying Yu. "This technique will help get these cells to the clinic a lot sooner."

However, the new approach would fail for patients with a genetic disease, because the stem cells would carry it.

Other hurdles remain. Despite the present wave of enthusiasm, investigators may find that the new cells are actually not embryonic stem cells. And the genes were transported with a virus, which carries its own set of dangers. "We need to develop an alternative system to deliver these genes," said Yu.

No matter how promising the new approach may be, Thomson does not see it as a reason to abandon research into embryonic stem cells, which remain the reference point for studying cellular specialization and development.

Nonetheless, by sidestepping embryos and human eggs, the new advance could accelerate the field of regenerative medicine. For one thing, labs and equipment that have received U.S. funding may now be used to study ES cells. And for another, "Any lab with standard molecular biology [tools] can do reprogramming without difficult-to-obtain oocytes [egg cells]," says Thomson.

- David Tenenbaum

Related Why Files
• The Why Files Guide to Stem Cells
• Stem Cell Progress Report
Theraputic Cloning
Political Science
Blood from a Stem Cell
Learning About Learning
Scientific Fraud

Bibliography
• Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells, Junying Yu et al, Science Express, Nov. 20, 2007.
• Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors, Kazutoshi Takahashi et al, Cell online, Nov. 22, 2007.


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