Reprogrammed Skin Cells Strut Their Stuff

ScienceNOW Daily News ^ | 6 December 2007 | Gretchen Vogel

[neverdem]

Corrected.
Blood from mice treated with iPS cells (above) does not show the sickle-shaped cells present in untreated mice (top).

Credit: J. Hanna et al., Science

Skin cells reprogrammed to act like embryonic stem cells--a breakthrough first reported in human cells 2 weeks ago--are already showing promise as a therapeutic agent. In today's online edition of Science, researchers describe using induced pluripotent stem (iPS) cells to alleviate symptoms of sickle cell anemia in mice. The technique is not yet safe to try in people, but scientists say it is proof of principle that iPS cells could someday treat human disease.

Induced pluripotent stem cells excite scientists because they represent a way to obtain custom-made stem cells without the ethical hurdles of using embryos or oocytes (ScienceNOW, 20 November). Researchers hope that they might be able to use the technique to replace faulty cells in the body with healthy cells containing the patient's own DNA.

Tim Townes of the University of Alabama, Birmingham, and his colleagues wondered whether iPS cells might prove useful in a mouse model of sickle cell anemia. (Blood cells are much easier to replace than are cells that make up tissue.) In afflicted humans, red blood cells become curved and can't easily flow through blood vessels. The mice show many of the symptoms that human patients do, and so they were an especially good candidate to test iPS cells' abilities, says stem cell researcher Rudolf Jaenisch of the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology, both in Cambridge, who collaborated with Townes on the project.

The first step was creating iPS cells specific to the mice. The researchers took skin cells from the tails of sickle cell mice and inserted copies of four genes that made the cells take on the characteristics of embryonic stem cells. They also added a corrected hemoglobin gene into the cells and coaxed them into becoming blood-producing stem cells. Finally, the researchers injected these partially differentiated cells into sickle cell mice that had been treated with radiation to kill their own blood stem cells. Within a few weeks, the new cells were producing mature blood cells, and the symptoms of sickle cell disease had dramatically improved, the team reports.

Townes says he and Jaenisch initially collaborated on a project that used nuclear transfer to make corrected stem cells, a process called therapeutic cloning. But the experiments failed, he says, because nuclear transfer was too inefficient to produce the needed cells. The iPS cell technique "is amazingly efficient," he says.

The paper is an important step forward, says Jose Cibelli of Michigan State University in East Lansing. The lab results for iPS cells have been impressive so far, he says, "but if they do not have therapeutic value, they will be far from getting to the point of replacing the whole idea of therapeutic cloning."

The important next step for the field, Cibelli says, is to find reliable ways to differentiate the cells into a variety of useful cell types and to be sure that no undifferentiated cells remain to cause potential tumors. Other experiments with iPS cells have suggested that they might be prone to causing cancer, but none of the treated mice showed any signs of tumors after 12 weeks. That is a promising sign, Townes says, but much longer studies would be needed before the technique could be considered safe enough to try in humans.

Related site

• More on sickle cell anemia

[Moonman62]

The Iraq war is going much better, and there’s no longer a need for embryonic stem cells. The liberals must be more depressed than usual.

[neverdem]

iPS cell ping

[Reaganesque]

Wow! We live in very, very interesting times!

[SuziQ]

The news just seems to get better and better about uses of these IPS cells!

[hocndoc]

And now, for the fine print:

To reduce the potential risk of tumor formation due to c-Myc transgene expression (13), iPS cells were infected with an adenovirus encoding Cre-recombinase to delete the lentivirus transduced c-Myc copies. One out of 10 iPS subclones (iPS #3.3) had deleted both transduced copies of c-Myc and was used for further experimentation (Fig. 2C).