Sickle Save: Skin cells fix anemia in mice

Using a new technique to turn skin cells into stem cells, scientists have corrected sickle cell anemia in mice. The advance provides proof of principle that stem cells made without embryos can treat disease, at least in lab animals, says Rudolf Jaenisch, the biologist who led the work at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

Jaenisch and his team caution, however, that the technique is not yet suitable for use in humans because it may cause tumors.

Still, Jaenisch says that embryofree stem cells now “have the same potential for therapy as embryonic stem cells, without the ethical and practical issues.” Embryonic stem cells are difficult to obtain, and some people oppose such research because it destroys discarded embryos.

In the new work, the scientists turned skin cells into embryonic-like cells. Researchers at Kyoto University in Japan first developed the technique in mice and published the protocol last year. Last month, two teams repeated the feat with human cells (SN: 11/24/07, p. 323). All of these protocols deploy viruses carrying four master genes that turn back the clock on skin cells, making them look and act embryonic. Researchers call these new cells induced pluripotent stem (iPS) cells because they can form any tissue in the body.

The Whitehead researchers obtained mice engineered to carry a defective version of the human hemoglobin gene. That flaw distorts red blood cells into the characteristic sickle shape. To fix the flaw, the researchers induced skin cells plucked from the tails of the mice to become iPS cells, and corrected the genetic defect.

Next, the Whitehead team prodded the corrected cells into becoming blood stem cells, which can produce red and white blood cells. The team used a recipe originally developed for embryonic stem cells and found that it also made iPS cells grow into blood stem cells, the researchers report online Dec. 6 and in an upcoming Science.

“We wanted to compare the embryonic stem cells versus the iPS cells,” says Whitehead researcher Jacob Hanna. “They behaved similarly.”

Finally, the researchers performed a procedure akin to a bone marrow transplant. They transfused a million of the corrected blood stem cells into each of three mice whose bone marrow—which harbored the mice’s original defective blood stem cells—had been obliterated by radiation. The corrected blood stem cells soon began producing healthy red blood cells. Because the same animal was both donor and recipient, the infused cells were not rejected, as commonly occurs in human bone marrow transplants.

After this treatment, the formerly lethargic mice made swift recoveries. “The improvement was profound,” says Hanna. “There was a clear sign of reduction of destruction of red blood cells, which is actually the main problem in sickle cell anemia.”

Mark Walters, a bone marrow transplant specialist at Children’s Hospital and Research Center in Oakland, Calif., says the procedure surmounts the biggest obstacle in performing such transplants in children—finding a genetically matched donor. Worldwide, only 300 to 400 children with sickle cell anemia have received bone marrow transplants because matched siblings are rare. “But the results are outstanding, with a cure rate between 85 and 90 percent,” Walters says.

Before the procedure can advance to human trials, though, researchers must find a more benign way to make iPS cells, because the viruses currently used can trigger cancer. “We’d have to have some information that these are not preleukemic or premalignant cells, that they’re safe in the long term,” says Walters.