December 3, 2007

Versatile Human Stem Cells Created Without Embryos

Two separate research teams have figured out how to "reprogram" cells with just a handful of genes to give them the characteristics of embryonic stem cells. The breakthrough may eventually put to rest the ethical controversy surrounding stem cells.

Human embryonic stem cell lines have the ability to form virtually any cell type in the body and can grow indefinitely in the laboratory. Many researchers have been hoping to learn how to harness the potential of these cells to repair tissues and organs throughout the body. However, the cells have been controversial because isolating them entails destroying an early human embryo.

Last year, researchers in Japan developed a way to reprogram cells from adult mouse tail skin so that the cells, like embryonic stem cells, can be coaxed into becoming different cell types. The team was able to accomplish the feat by adding 4 key genes. The research progressed rapidly from there, with teams in both Japan and the U.S. showing that they could create live mice using the reprogrammed cells earlier this year.

A team led by Dr. James A. Thomson of the University of Wisconsin, Madison reported in the online edition of Science on November 20, 2007, that they were able to reprogram human cells in a similar way. They used 4 genes, 2 of which were different from the ones used by the Japanese team. The Japanese team also reported on the same day in Cell that they had figured out how to apply their technique to human cells.

Thomson's team—funded by NIH's National Center for Research Resources (NCRR) and National Institute of General Medical Sciences (NIGMS), along with the Charlotte Geyer Foundation—selected 14 promising genes to test in cells derived originally from fetal skin. Through a process of elimination, they narrowed the number of genes required to reprogram the cells down to 4. They then used the 4 genes to successfully reprogram a widely studied cell type taken from the foreskin of a newborn boy.

The Japanese group, in its study, was able to reprogram cells taken from 2 adults. One of the 4 genes they used, however, is known to cause cancer, so its therapeutic uses may be limited.

Many major technical hurdles remain before these types of reprogrammed cells can be used in therapies. Looming large is the challenge of how to guide these cells into becoming other cell types. More immediately, both research teams used a kind of virus to deliver the genes that can disrupt a cell's DNA and cause cancer; the researchers will have to develop another way of getting these genes into cells. It also remains to be proven that these cells aren't different in clinically significant ways from embryonic stem cells.

Despite these challenges, this major advance could open doors to innovative therapies in the future, where people's own cells might be reprogrammed and used to repair their damaged tissues and organs.
—by Harrison Wein, Ph.D.

Related Links:

• Stem Cell Basics:
  http://stemcells.nih.gov/info/basics