Stem cells created without embryos
Published Wednesday, November 21, 2007 12:15PM EST
Scientists have made a startling breakthrough that allows them to "reprogram" ordinary skin cells to act like embryonic stem cells.
Stem cells are considered the body's ultimate master cell, able to become almost any other kind of cell, such as heart or lung cells. They have thus been called "pluripotent," meaning they have the ability to differentiate into other cell types.
Until now, the best source of stem cells has been from cloning cells from discarded human embryos. But the use of embryos has been fraught with ethical questions. Now, two new studies suggest there may be an easier way.
On Tuesday, it was announced that laboratory teams working on two continents have both been able to publish landmark studies on the use of skin cells to create pluripotent stem cells that look and act like embryonic stem cells.
They call the cells "induced pluripotent stem cells," or iPS cells for short.
Dr. Janet Rossant, chief of research at Ottawa's Hospital for Sick Children, said the findings are a "very important step forward."
"You take the cell that has become quite specialized, making skin in this case, and by changing the genetic environment you can take the cell and make it think it's back in the embryo and it has the full potential to make every cell in the body," Rossant told CTV's Canada AM on Wednesday.
She said there are still major questions about the research and how it will effect treatment for serious diseases such as diabetes or Parkinson's, noting it needs to be clear the cells will not create tumours or disorganized tissue in patients.
Rossant said some cancer-related effects were detected in the testing, and the process still needs to be fine-tuned.
"On the other hand, this whole process already tells us we should be able to make cells we can study in a petri dish, cells from people who have serious disease, and be able to understand the biology of that diseases in a petri dish and develop new drugs and treatments right there in the dish that you could later test in people."
The findings may have political repercussions in the United States, where President George Bush rejected bills that would have funded embryonic stem cell research.
He had said that medical breakthroughs were possible without destroying embryos. Democrats had said that because of Bush's ideological beliefs he had blocked research that could have uncovered cures to diseases afflicting millions of people.
The authors of the study note that iPS cells are similar -- not identical -- to embryonic stem cells and differences have been noted. But more research is needed to determine what those differences mean.
The two studies are published in two journals: Science and Cell. The Cell paper is from a team led by Dr. Shinya Yamanaka of Kyoto University; the Science paper is from a team led by James Thomson and Junying Yu of the University of Wisconsin in Madison.
Both studies detail a "direct reprogramming" recipe that includes just four ingredients to transform ordinary skin cells, called fibroblasts, into iPS cells.
Yamanaka's team introduced the genes OCT3/4, SOX2, C-MYC, and KLF4 to get their iPS cells. The Thomson team used a slightly different cocktail: OCT4, NANOG, SOX2 and LIN28.
Yamanaka's team reports that they were able to use iPS cells to produce cardiac muscle cells. After 12 days of growth in laboratory dishes, the clumps of cardiac muscle cells actually started beating.
Technique far from perfect
But neither Yamanaka's nor Yu's recipe is perfect. The technique involves using a retrovirus to deliver the genes into the skin cells, which in turn disrupts the DNA of the skin cells. That creates the potential for developing cancer.
But the DNA disruption is just a byproduct of the technique, and experts say they believe it can be avoided.
Thomson, who also produced the first successful human embryonic stem cell lines in 1998, admits that a lot more research is needed on this new technique, "but these methods should be useful for developing disease models and for drug development," his team wrote.
Ian Wilmut of the Scottish Centre for Regenerative Medicine at the University of Edinburgh, who helped clone the first mammal in 1997, Dolly the sheep, said the findings are hugely significant.
"We can now envisage a time when a simple approach can be used to produce stem cells that are able to form any tissue from a small sample taken from any of us," Wilmut said in a statement.
"This will have enormous implications for research and perhaps one day for therapy."
The therapeutic implications of the research are likely years away. Besides overcoming the DNA disruption obstacle, scientists still have to answer basic questions about these cells.
In the short term, these cells would probably be used first for lab studies to create artificial human tissues to test potential drugs.
Scientists also say it's still important to pursue the strategy of using cloned cells from embryos.
The hope is that one day, scientists can use stem cells to treat a variety of diseases, including creating brain cells for Parkinson's disease, pancreatic cells for diabetes and nerve cells for spinal-cord injuries.
The new iPS techniques would likely qualify for federal research funding in the U.S., unlike projects that extract stem cells from human embryos for which funding has been strictly limited.
The iPS cell work would also likely win the approval of bioethicists and religious leaders.
R. Alta Charo, a University of Wisconsin-Madison professor of law and bioethics, says this research alters the debates surrounding both human embryonic stem cell research and human cloning.
"This is a method for creating a stem cell line without ever having to work through, at any stage, an entity that is a viable embryo," Charo says. "Therefore, you manage to avoid many of those debates with the right-to life community."
With files from The Associated Press