Researchers at UAB, along with a team from the Whitehead Institute, have reported successfully treating sickle cell anemia in mouse models using induced pluripotent stem (iPS) cells. The findings, published in Science Express Online Dec. 6, are the first to actually use the iPS technique to treat disease in an animal model.

UAB researcher Tim Townes has successfully treated sickle-cell anemia in mouse models using genes to reprogram the blood stem cells.

“The UAB/Whitehead teams took skin cells from mouse models genetically engineered to have sickle-cell disease and reprogrammed them into iPS cells by adding four genes to each cell,” said Tim M. Townes, Ph.D., chair of the Department of Biochemistry & Molecular Genetics and co-senior author of the study. “The new genes remodeled the chromosomes that instruct a skin cell to be a skin cell, so that the cells revert to stem cells.”

The researchers then used a DNA fragment engineered by Townes’ laboratory in 2006 to correct the basic sickle mutation. The corrected iPS cells then were induced to become blood stem cells (capable of making any type of blood cell) and were transplanted back into the diseased mice.

“The new blood stem cells began to function properly, making normal red blood cells that did not sickle,” Townes said. “The animals showed no symptoms of the disease and did not reject the transplanted cells.”

Previous work with iPS cells showed simply that the process worked, and skin cells could be transformed into stem cells. Townes and colleague Rudolf Jaenisch of the Whitehead Institute, a professor of biology at MIT and co-senior author of the study, say this “proof of principle” is the first example of creating iPS cells derived from a disease model and using these cells to correct a genetic mutation and treat a disease.

“These findings are a major step forward in developing a cure for sickle-cell anemia,” Townes said. “We anticipate that this therapy will work in humans as it works in mice. And it cured sickle cell in mice.”

There are obstacles to be overcome. The added genes that transform regular cells into iPS cells are delivered by retroviruses, and there are inherent risks in the use of retroviruses. The process also uses a cancer gene to stimulate cell division – sort of like a starter for sourdough bread. That gene has to be regulated, so it does not stimulate uncontrolled cell division, potentially causing a risk for cancer. Townes says researchers are already at work in resolving these issues, although it may be years before iPS is a viable approach to treat disease in humans.

This research was funded by the National Heart, Lung and Blood Institute, one of the National Institutes of Health (NIH).