Skin cells fix anemia in miceUsing 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.
More abstracts about the Skin cells fix anemia in mice