Safer, Ethical Procedure Found to Produce Stem Cells

Stem cell therapy has become the subject of huge interest and vigorous debates. Promoters believe stem cells offer great promise for new medical treatments to combat cancer, diabetes, Alzheimer’s and other regenerative diseases, while the opposition argues that research on embryos—the prime source of the most versatile stem cells, pluripotent—destroys human life. In the past year, scientists have found genes that can transform ordinary skin cells into cells that look and act like embryonic stem cells, eliminating the use of an embryo, and the ethical concerns. The downside is that delivery of these genes requires the use of a virus, raising concerns the cells could cause tumors or other effects if placed in a patient. Now, researchers say they have discovered a new method of transporting the genes without the use of such potentially harmful viruses, thereby overcoming a major hurdle for safe, personalized stem cell therapies in the future.

In the new work, researchers in Toronto and at the University of Edinburgh instead used a piece of DNA called a transposon, which can insert itself into an organism’s DNA and carry a cargo with it, to deliver four specific genes. In this case, the transposon version used is called “piggyBac,” which has been used to genetically modify a range of organisms. After the conversion, the added DNA was removed from the transformed cells with a specific enzyme. The researchers used the technique in both mouse and human skin cells and found the reprogrammed cells—iPS cells—behaved just like embryonic stem cells. “PiggyBac carries the four genes into the cells and reprograms the cells into stem cells. After they have reprogrammed the cells, they are no longer required, and in fact they are dangerous,” explains Dr. Andras Nagy, senior investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, Canada. “After they do their job they can be removed seamlessly, with no trace left behind. The ability for seamless removal opens up a huge possibility.”

In 2005, Nagy created Canada’s first embryonic stem cell lines from donated embryos no longer required for reproduction by couples undergoing fertility treatment; research that played a pivotal role in his current discovery. One of the critical components reported in Nagy’s paper, published in the March 1, 2009 issue of Nature, was developed in the laboratory of Dr. Keisuke Kaji from the Medical Research Council (MRC) Center for Regenerative Medicine in Edinburgh, Scotland. “I was very excited when I found stem cell-like cells in my culture dishes. Nobody, including me, thought it was really possible,” Kaji said. “It is a step towards the practical use of reprogrammed cells in medicine, perhaps even eliminating the need for human embryos as a source of stem cells.”

“It’s very exciting work,” said Robert Lanza, a stem cell researcher at Advanced Cell Technology in Worcester, Massachusetts. “With the new work, we’re only a hair’s breadth away from the biggest prize in regenerative medicine—a way to create patient-specific cells that are safe enough to use clinically.”

Other scientists, however, while crediting the work as an important advance, say it remains crucial to continue work on both types of cells. “The point is, we don’t know yet what the end potential of either of these approaches will be,” said Mark A. Kay of Stanford University. “No one has cured any disease in people with any of these approaches yet. We don’t know enough yet to know which approach will be better.”

In 2001, President George W. Bush restricted federal funding for human embryonic stem cell research to prevent taxpayer money from encouraging the destruction of human embryos, which is necessary to obtain pluripotent cells. However, Senators Tom Harkin, an Iowa Democrat, and Arlen Specter, a Republican from Pennsylvania, have reintroduced a Senate bill that would allow federal funding for research using stem cells taken from human embryos left over from fertility treatments. “For too long, political interference has delayed research that holds the promise for millions of Americans who suffer from a wide range of diseases,” Harkin said in a statement. “President Obama has promised to lift the restrictions on embryonic stem cell research that were put in place by President Bush, and I hope and expect that he will do so soon, but we have to make sure that the freedom to pursue this research is also protected by federal law, not merely by an executive order that can be reversed during a future administration.”