Researchers Say New Stem Cell Technique Cures Sickle Cell in Mice

Newswise — Researchers at UAB (University of Alabama at Birmingham), along with a team from the Whitehead Institute, report successfully treating sickle cell anemia in mouse models using induced pluripotent stem (iPS) cells, a new stem cell technique that uses skin cells and does not require embryos. The findings, published in Science Express Online on Dec. 6, are the first to actually use the iPS technique to treat disease in an animal model.

The iPS technique received widespread attention in November when two laboratories reported using the process to turn human skin cells into stem cells, cells which can then be induced to form any other type of cell. Scientists believe stem cells have great potential in treating a variety of human diseases.

"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., professor and chair of the Department of Biochemistry and Molecular Genetics at UAB 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 in the cells. The corrected iPS cells were then 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, Ph.D., with the Whitehead Institute and 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).