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Reprogrammed Human Stem Cells Clear Another Hurdle

Skin cells have been induced into a pluripotent state, giving them the versality of embryonic stem cellsJunying Yu, University of Wisconsin-Madison.

Researchers have developed a technique in which the genes used to reprogram human cells and give them the versatility of embryonic stem cells can be cleanly removed afterward. The advance takes researchers another major step toward creating cells that could potentially be used for human therapies.

Human embryonic stem cell lines are of keen interest to researchers because of their ability to grow indefinitely in the laboratory and potentially form almost any type of cell in the body. Many researchers have been hoping to learn how to use these cells to repair various tissues and organs. However, embryonic stem cells have been controversial because isolating them entails destroying an early human embryo.

Several research teams have been racing to develop ways to genetically reprogram other types of cells to give them the versatility of embryonic stem cells. A team led by Dr. James A. Thomson of the University of Wisconsin, Madison had previously succeeded in using only 4 genes to reprogram a widely studied cell type taken from the foreskin of a newborn boy. However, that technique delivered the genes via a virus that can disrupt a cell's DNA and cause cancer.

The same research team has now developed another way to create these kinds of cells, called induced human pluripotent stem cells. Rather than using a virus to deliver the genes, they turned to a circular piece of DNA called a plasmid. The plasmid and the genes it carries don't integrate into the cells' genome. The plasmid can also be screened out of subsequent generations of cells, creating cells that are free of any contaminating genetic sequences. The work was funded by NIH's ×îÐÂÂ鶹ÊÓƵ Center for Research Resources (NCRR) and ×îÐÂÂ鶹ÊÓƵ Institute of General Medical Sciences (NIGMS), along with the Charlotte Geyer Foundation.

The researchers reported in the online edition of Science on March 26, 2009, that they successfully used the method to create induced human pluripotent stem cells that are similar to human embryonic stem cells in their ability to proliferate and to develop into different cell types. The scientists experimented with several combinations of genes and found that a combination of 7 genes proved most effective. They believe there's still room for improving the technique.

"This latest discovery by Thomson's group of a new method for generating induced human pluripotent stem cells without inserting viral vectors into the cells' genetic material is a major advance toward safely reprogramming cells for clinical use," says Dr. Marion Zatz of NIGMS.

This advance could open doors to innovative therapies in the future, where people's own cells might be reprogrammed and used to repair damaged tissues and organs. However, researchers still face the significant challenge of learning how to efficiently guide these cells into all the different cell types that might be useful for regenerative medicine. It also remains to be proven that the cells aren't different in clinically significant ways from embryonic stem cells.

—by Harrison Wein, Ph.D.