/ 1 January 2002

Wresting the secrets from stem cells

A study that found adult blood stem cells were unable to transform themselves into other types of tissue raises new doubts about whether they could be used to reinvigorate ailing organs.

The finding supports the view that embryonic stem cells offer the most promise for treating such conditions as heart disease, spinal injury, diabetes and Parkinson’s disease, some researchers say. Many people, including President George Bush, oppose using human embryonic stem cells in medical research because it involves the death of an embryo.

Stanford University researchers attempted to trace the evolution of blood stem cells after placing them singly into mice whose bone marrow had been destroyed. The hope was that the study would show how a single blood-making cell could grow into millions of cells, including, perhaps, cells in other tissues of the body.

Instead, said Amy Wagers, first author of the study, the group found that the blood stem cells replenished the bone marrow but made almost no other types of tissue cells.

Wagers said the study strongly suggests that blood stem cells make only one thing – blood. Making skin, neurons, muscle or liver cells, as some researchers have reported from such stem cells, ”is an extremely rare event” that probably would not be useful in the treatment of disease, she said.

”We only had one neuron out of millions of cells,” said Wagers.

”With the liver, the frequency was only one in

70 000. It can happen, but it is not robust.”

The study, published in the current issue of Science magazine, is part of a new field of study directed toward regenerative medicine, which would cure or control disease by replacing flawed or worn-out cells with new cells grown from stem cells. Experts believe that stem cells may eventually be cultured into new tissue that would be used to replace or repair ailing or diseased organs.

Researchers in many labs are now studying two basic types of stem cells. Somatic, or adult, stem cells come from mature tissue.

Embryonic stem cells come from embryos that have been allowed to grow to a certain point and then killed to extract the cells. The Bush administration has put in place strict guidelines controlling the use of federal dollars for embryonic stem cell research, while putting no such restrictions on adult stem studies.

Some officials have argued that embryonic stem cell studies are not needed because of growing evidence that adult stem cells, when properly cultured, can grow into other tissue cells for medical treatment.

But the work of Wagers and others suggest that adult stem cells offer only an uncertain promise of ever being medically useful.

In the Stanford study, Wagers and her colleagues separated a single blood-making stem cell from the bone marrow of a mouse. They then inserted into the cell a gene that would cause it to make the cell and its progeny glow. Single copies of such cells were then injected into mice whose bone marrow had been killed by radiation.

After four to nine months, the tissue in the test mice was examined microscopically, with the researchers looking for evidence of the fate of the succeeding generations of the single injected cell.

Wagers said they found that the blood stem cells reconstituted the blood making tissues in the bone marrow, but had virtually no effect on other tissues in the body. She said they found one brain cell that glowed and only about seven in the liver.

”What our study shows is that the most robust and reproducible production of multiple tissues from a single cell comes from the embryonic stem cells” and not from adult blood stem cells, said Wagers.

Other stem cell researchers, however, say the issue is far from settled. Dr Dennis Steindler, a stem cell researcher at the University of Florida, said that the ”jury is still out” on which type of stem cell will be the most medically useful.

”There is still a great deal to learn about the possible use of adult stem cells for therapeutics,” he said. ”The field of regenerative medicine is just beginning. We have a lot of experiments we need to do to figure out the way that stem cells can be used to cure human diseases.”

He said that most experts believe that both adult and embryonic stem cell research should be continued vigorously. Steindler said is possible that both types of cells eventually will find a place in medicine and that prudence demands that both types of research continue. – Sapa-AP