|Arthur D. Riggs|
Human embryonic stem cells should undergo quality assessment before scientists use them, according to investigators from City of Hope and the University of California, Los Angeles. Their study appeared in the March 12 issue of Proceedings of the National Academy of Sciences.
The research team found that certain genes that are inactive in normal human embryonic stem cells actually were turned on in government-approved cell lines. No one can say for certain how the changes affect the cells, but reactivation of these genes indicates the stem cells are no longer normal and may not be ideal for many therapeutic or research uses.
By gauging the quality of human embryonic stem cells, researchers could identify in advance which cells are most likely to cause problems. Stem cells are “seed” cells that can transform into all other cell types. As they mature, they develop into the various tissues of the body.
Experts maintain that human embryonic stem cells may be the most useful form of stem cells. These cells come from early stage human embryos. Unlike so-called “adult” stem cells, which only last for a limited number of generations in the lab, embryonic stem cells are essentially immortal. They can grow for countless, if not infinite, generations. The immortality of stem cells is important to their potential therapeutic use.
“Most applications of stem cells aren’t intended to use them at their earliest stage,” said Arthur D. Riggs, Ph.D., director emeritus of Beckman Research Institute. Instead, researchers or clinicians will grow the embryonic stem cells into the desired tissue type and then use those matured cells for therapy or research. Embryonic stem cell lines provide an unlimited, stable source for these cells.
The study indicates most if not all of the human embryonic stem cell lines that the
National Institutes of Health approved for government-funded use exhibit unusual characteristics, and some are clearly irregular. Only 19 usable embryonic stem cell lines are currently approved for use in the United States.
Riggs noted one particular defect in the cells.
“We found that existing female human embryonic stem cells are likely to be abnormal with regard to X-chromosome inactivation,” he said.
X chromosomes contain genes that determine the sex of an individual. Female cells have two X chromosomes; men have one X and one Y chromosome. For female cells to behave normally, one of the two X chromosomes must be inactive.
Cells turn off one copy of an X chromosome through epigenetic mechanisms — processes that modify DNA’s function.
The recent study found that, while all cell lines were abnormal, some clearly showed partial reactivation of the X chromosome that was supposed to be dormant. Scientists cannot entirely predict the effects of this partial reactivation, but they believe it could significantly hurt the cells’ usefulness.
Riggs believes all human embryonic stem cell lines should undergo analysis to determine their epigenetic status. He is working with Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology, to develop a method to do so.
Riggs has been studying epigenetics for nearly 40 years. The National Academy of Sciences recently elected him a member due in large part to his pioneering work in the field.
In August 2001, President George W. Bush prohibited any federal funding for research involving human embryonic stem cells research outside of already existing embryonic stem cell lines. He made the controversial decision due to moral concerns over the destruction of human embryos.