Mice with Sickle Cell Anemia Cured with New iPS Cells

By Julie Steenhuysen, Reuters, December 6, 2007

Proving in principle that a new form of stem cell could be used as a therapy, on Thursday, U.S. researchers treated mice with sickle cell anemia using the cells which were made from ordinary skin cells.

Possessing the same characteristics as embryonic stem cells, skin cells were reprogrammed by Japanese and U.S. researchers last month. The cells were named "iPS" cells, short for "induced pluripotent stem cells".

Using mouse skin cells, the Japanese researchers had initially accomplished the same feat prior to using human skin cells.

A defect in a single gene causes the blood disease called sickle cell anemia. Mice were engineered to have this condition by a research team at the Whitehead Institute of Biomedical Research in Cambridge, Massachusetts. They team successfully treated these mice withe the new iPS cells.

"This is the first evaluation of these cells for therapy," said Dr. Jacob Hanna, who worked on the study. "The field has been working for years on strategies to generate customized stem cells," he added in a telephone interview.

Hanna said that the need for immune suppression or donor matching would be eliminated by creating stem cell therapies from a person's own cells since that would make them genetically identical.

"Now, with the breakthrough of this new method for generating stem cell-like cells, can we try to substitute a diseased tissue in a living animal?"

Four genes were inserted into the mice skin cells by Hanna and colleagues working in Rudolf Jaenisch's lab at Whitehead Institute. This action transformed them into iPS cells.

"We call it the magic four factor," Hannah said.

Cells that can morph into any type of cell in the human body are called multipurpose or pluripotent. Examples of these cells are embryonic stem cells and the new iPS cells.

The researchers substituted the faulty gene that causes sickle cell anemia with a working one after coaxing these mouse master cells into becoming blood-forming stem cells.

The journal Science reported on Friday that tests showed normal blood and kidney function after the scientists transplanted these cells into the diseased mice.

"This demonstrates that iPS cells have the same potential for therapy as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells," Jaenisch said in a statement.

Still, much work remains in order to perfect the technique.

A type of virus called a retrovirus is used to deliver the four genes needed to turn skin cells into master cells.

"Once they enter the genome, there is the danger that they can silence some genes that are important or they can activate some dangerous genes that shouldn't be activated," Hanna said.

c-Myc, which is one of the genes, is known to cause cancer, and this presents another obstacle for researchers to overcome.

After the gene had completed it's task of transforming the skin cells into iPS cells, Hanna and colleagues actually removed the c-Myc gene to get around the potential problem.

The new technique will make stem cells much easier to study. Spinal injuries, Parkinson's disease, diabetes, and other conditions could all be treated someday using the new iPS cells.