WASHINGTON - Using a newly developed technique for turning skin cells into stem cells, scientists have cured mice of sickle cell anemia - the first direct proof that the easily obtained cells can reverse an inherited, potentially fatal disease.
Researchers said the work, published online yesterday in the journal Science, points to a promising future for the novel cells. Known as iPS cells, they were announced to great fanfare last month and have been touted by President Bush and some scientists as a possible substitute for embryonic stem cells, which have been mired for years in controversy.
But researchers also cautioned that aspects of the new approach would have to be changed before it can be tried in humans. Most important, the technique depends on the use of gene-altered viruses that have the potential to trigger tumor growth.
"The big issue is how to replace these viruses," said Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Mass., a leader of the new study.
Induced pluripotent stem (or "iPS") cells are virtually identical to embryonic stem cells. They can morph into all of the more than 200 cell types in the body but are derived from skin, not embryos. Mouse iPS cells were first derived this year; last month's breakthrough was for human skin.
The new experiment got iPS cells from the tail tips of mice sick with sickle cell anemia, which can cause painful circulatory problems, kidney failure and strokes.
Using DNA splicing techniques, the researchers then snipped out the small mutated stretches of DNA that cause sickle cell disease and filled those gaps with bits of DNA bearing the proper genetic code.
They next treated the iPS cells with another virus - this time one designed to induce a genetic change that encouraged them to mature into bone marrow cells.
Finally, each mouse that gave up a few skin cells at the beginning of the experiment was given an infusion with the corrected marrow cells created from its own skin. Those cells set up permanent residence in the animals' bones and began producing blood cells - the major function of marrow - and releasing them by the millions into the circulatory system.
"All the parameters we can measure are now normal," Jaenisch said. "The mice are cured."
People with sickle cell disease can be cured with bone marrow transplants, but only about 20 percent of patients have a healthy sibling whose tissue type is a close enough match. Even then, 20 percent of transplants fail, and they sometimes result in a potentially deadly reaction.
Those problems don't arise with iPS transplants because the cells are genetically identical to the animals getting them. Tests indicate 80 percent of each mouse's marrow is now made up of new cells. Four months after treatment, no tumors have been seen.