Researchers Make More Advances With Adult, iPS Stem Cells Than Embryonic

Bioethics   |   Steven Ertelt   |   Oct 13, 2008   |   9:00AM   |   WASHINGTON, DC

Researchers Make More Advances With Adult, iPS Stem Cells Than Embryonic

by Dr. David Prentice
October 13, 2008 Note: Dr. David Prentice is Senior Fellow for Life Sciences at Family Research Council. Up to July 2004 he had spent almost 20 years as Professor of Life Sciences, Indiana State University, and Adjunct Professor of Medical and Molecular Genetics, Indiana University School of Medicine.

Scientists in Germany have shown that adult stem cells with the same flexibility as embryonic stem cells can be grown from human testes tissue. Like embryonic stem cells and iPS (induced pluripotent stem) cells, these human stem cells are pluripotent, showing the ability to grow for long periods in the lab and to form representatives of most or all tissues of the body.

This is not the first report of pluripotent stem cells from testes.

A different German team had previously published their results producing such flexible stem cells from mouse testes, and a U.S. group had also published their results producing these flexible stem cells from mice, while a U.S. company had claimed they were able to produce flexible stem cells from human testes.

However, this German group is the first to publish evidence (online in the journal Nature) that such cells can be made from human testes tissue.

According to senior author Thomas Skutella, "The advantage these cells have in comparison to embryonic stem cells is that there is no ethical problem with these cells and that they are natural."

Skutella is a professor at the Center for Regenerative Biology and Medicine in Tuebingen, Germany.

Meanwhile, Dr. Shinya Yamanaka and his team have done it again. This time they have produced induced pluripotent stem cells (iPS cells) without using viruses.

Yamanaka was the first to show that stem cells equivalent to embryonic stem cells could be produced from normal cells such as skin, without ever using human embryos or human embryonic stem cells in his research. The process involved adding four genes to cells using retroviruses. The added genes "reprogram" the gene expression of the normal cells, making them behave like embryonic stem cells, but without the use of embryos, eggs, or cloning.

However, there has been some concern that the retroviruses, which integrate into the cell’s DNA, have the potential to induce cancer (beyond that usually seen with embryonic stem cells.)

Yamanaka has now accomplished in mouse cells the reprogramming without the use of any virus, by using plasmids (circular pieces of DNA.) Using the same four genes, the cells were reprogrammed to iPS cells and behaved like embryonic stem cells, but without any of the added DNA integrating into the cell’s DNA.

Published online 9 October by Science, this advance continues the avalanche of results for iPS cells seen in just the last year, emphasizing the lack of results with embryonic stem cells as well as the growing movement away from the use of embryos and cloning.

Also, researchers at Harvard announced October 12 that they have produced flexible, embryonic-like iPS cells (induced pluripotent stem cells) by adding only two genes and "sprinkling" a helping chemical onto cells.

The iPS cell method, first developed by Dr. Shinya Yamanaka of Japan in 2006, involves adding four genes (via viruses) to "reprogram" normal cells so that they behave like embryonic stem cells, but without the use of embryos, eggs, or cloning.

The race has been on to simplify the reprogramming process, using fewer genes and safer viruses, or no viruses at all. Over the last ten months, numerous groups have reported improved methods and use of fewer genes, including a recent published report using safer viruses that deliver the genes and then disappear.

Meanwhile other researchers have been attempting to use simple chemicals or proteins to accomplish reprogramming, rather than using any DNA.

Previous work has used soluble proteins with three genes, and a combined genetic and chemical approach.

Now Doug Melton’s group, building on their previous work with making mouse iPS cells, has demonstrated that human iPS cells can be produced by adding only two key genes along with a simple chemical. They eliminated the need for potential cancer causing genes, adding only the two genes Oct-4 and Sox-2, both master regulators of stem cell gene expression.

The chemical additive, valproic acid, acts on the DNA-protein complex in the nucleus of cells to open its structure, making reprogramming easier.

While the method they used for this study still involves viruses to deliver the genes, Melton noted that "This study demonstrates there’s a possibility that instead of using genes and viruses to reprogram cells, one can use chemicals," and "These results support the possibility of reprogramming through purely chemical means."

With the rapidly-increasing number of researchers moving into the cell reprogramming field and away from use of embryos and cloning, it shouldn’t be long before the possibility is realized.

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