Skin Morphed Into Stem Cells, Now With Sickle Cell Mutations

Researchers for the first time say they've made stem cells with a disease-causing mutation -- in this case, sickle cell anemia, a genetic blood disorder that affects mostly people of African descent.
Scientists from Johns Hopkins University School of Medicine used a two-year-old method for giving adult skin cells the unlimited potential of those from a human embryo. To create the mutation, they modified the technique by adding an extra gene to a four-gene combination that reprogrammed the cells to their more primitive state. The extra gene boosted the efficiency of the process as much as 70-fold, making more stem cells in less time.

The refinements are a step toward enabling scientists to take cells from people with a genetic illness and make stem cells that match their condition. The cells could then be used to test drugs for possible treatments. Ultimately, the genetic flaws in the cells might be fixed and the modified cells transplanted into the patient to try to cure the disorder.

``The cells we generate may be useful for screening drugs and to understand the pathology of this disease,'' said Linzhao Cheng, a researcher at the Johns Hopkins Institute for Cell Engineering who led the study, published in the journal Stem Cells. ``In the long run, it offers the possibility that you may be able to do the gene correction through gene therapy.''

Because the cells came initially from the patient being treated, there would be little risk of the person's immune system rejecting the cells, Cheng said yesterday in a telephone interview.

Safety Concerns

While adding another gene may improve the efficiency of morphing cells into their more flexible state, it increases the risk that the genes used to transform the cells could trigger cancer or other problems when they integrate into the cell's DNA, said Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Institute in La Jolla, California.

``Why would anyone do it?'' Loring asked in an e-mail. ``We're already worried about reawakening of oncogenes'' -- genes that cause cancer -- ``so why would anyone want to add another one? I don't see the value in it.''

Loring said the report is likely to be one of many to come as researchers around the world use the cell-morphing technique developed by Shinya Yamanaka of Kyoto University in Japan to make cells that carry the genes that cause inherited conditions. Yamanaka called these transformed cells ``induced pluripotent stem cells,'' or IPS cells.

``It was clear from the first report of Yamanaka's discovery, that making pluripotent stem cells from individuals will be a booming business -- not just for scientists, but for entrepreneurs and patient advocates,'' she said.

While the method may bring advances, ``I have to urge caution,'' she said. ``We have to put safeguards in place to ensure that new cell lines that are made are as safe as, or safer, than human embryonic stem cells.''

Sickle Cell

Sickle cell anemia is a condition, triggered by mutations in a single gene that causes red blood cells to become sickle- shaped, instead of round. This leaves the cells unable to travel easily through the body's blood vessels, blocking flow to limbs and organs, causing pain, infections and organ damage.

In the U.S., the condition affects about 70,000 people, mostly of African descent. It also strikes people whose families come from south and central America, Caribbean islands, some Mediterranean countries, India and Saudi Arabia, according to the U.S. National Institutes of Health.

Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease in San Francisco said the report was the first to his knowledge in which a researcher published their success in making IPS cells carrying a genetic mutation.

``Most people are making them and trying to understand something about the disease before publishing,'' he said in a telephone interview .

Srivastava is engaged in an effort to make IPS cells from patients with genetic types of heart disease.