Stem cells have normal gene expression

BALTIMORE, July 8 (UPI) -- A new study shows for the first time human stem cells derived from embryos have normal gene expression, bolstering their potential for treating disease and abating previous concerns based on mouse studies suggesting the gene regulation process in these cells may be dysfunctional.

Previous studies using mouse stem cells derived from embryos had shown dysfunctional gene regulation and some scientists used this finding to argue human cells would exhibit the same characteristic and therefore could not be used in stem cell therapies, Andrew Feinberg, principal investigator of the study and a professor of medicine at Johns Hopkins University School of Medicine, told United Press International.

No one had conducted a study using human cells to see if this was the case, however. Feinberg's team did just that and found the human cells, called embryonic germ cells, behaved normally with correct gene expression. Embryonic germ cells are different from embryonic stem cells because they are derived from an embryo much later in development. But both types of cells have the potential to become any type of cell in the body and to cure diseases ranging from Parkinson's to diabetes.

The cells approved by the Bush administration for research purposes and contained in the National Institutes of Health's registry are embryonic stem cells. No one has yet looked to see if these cells have proper gene expression, but Feinberg said his group plans to study this.

At issue was a process known as imprinting in which a cell decides which of two copies of a gene it will express based on whether it originated with the mother or the father. Normally, only one copy of a gene should be expressed. This process appeared to be dysfunctional in mouse cells, resulting in incorrect gene expression that could lead to cancer or other problems. The situation argues against using the cells in therapy.

The reason the problem might have been seen in mouse cells and not in humans is that the mouse cells came from inbred lines of mice. In addition to the experiments with human cells, Feinberg's team cross-bred two lines of mice to remove some of the inbred genetics. They found the resultant embryonic germ cells exhibited gene expression that mostly was normal.

Using inbred strains of mice was not the right way to determine if embryonic germ cells had proper gene expression, Feinberg said. He noted he is not certain whether human embryonic stem cells will show proper gene expression.

Carmen Sapienza, professor of pathology at the Fels Institute for Cancer Research at Temple University in Philadelphia, who wrote a commentary on the study, said, "The prediction would be that you wouldn't see proper gene imprinting" in embryonic stem cells.

Sapienza argues imprinting may not be completely "hardwired" into the genes until further along in development, so the process still may be dysfunctional in the earlier-derived embryonic stem cells. If so, Sapienza told UPI, it would be unethical to use these cells to treat diseases in humans because dysfunctional genes could cause cancer or other problems.

Large political and ethical issues are imbedded in this issue. Although embryonic stem cells come from 3- to 4-day-old embryos, embryonic germ cells are derived from an even more controversial source: 5- to 11-week-old embryos. This may spur an argument for proceeding with adult stem cells, which are derived from tissues in adults and do not require destruction of embryos, as is the case with embryonic stem cells.

Some researchers have had success at getting adult stem cells to develop into a variety of cell types, but they do not appear to be as flexible as embryonic stem cells.

As Sapienza noted, "I wouldn't want to abandon embryonic stem cells until adult stem cells really are proven to be as pluripotent as people say they are."

Feinberg disagreed, however. "One of the arguments for using adult stem cells was because of the alleged imprinting problems," he said, adding the current study shows that argument is spurious. It is easier to drive embryonic stem cells to become a particular cell type than it is to do the same thing with adult stem cells, he said.

The study is scheduled to appear in the online edition of the Proceedings of the National Academy of Sciences during the week of July 8.

(Reported by Steve Mitchell, UPI medical correspondent, in Washington)