Scientists get cells to shift identities, raise new hopes

"This is just the beginning and we don't really know exactly what it means," said Dr. Evan Snyder of Harvard Medical School and Boston Children's Hospital, who discovered brain stem cells 15 years ago, the first such cells to be found in a solid organ. "There's an enormous amount of work to be done to prove that we're not simply being fooled by things we see in tissue cultures."

But Snyder's discovery appears to shatter a major tenet of biology--that once nature created an organism, the blueprint was carved in stone. A brain cell was always a brain cell and interchanging roles between stem cells was forbidden.

"Once we and others discovered that there was such a thing as a stem cell in an organ as rigid as the brain, that implied an enormous amount of flexibility," he said. "Maybe a liver stem cell can become a brain stem cell, and a brain stem cell can become a liver stem cell. That's the stage we're going through right now in terms of development."

Although many molecular biologists believe stem cell research began in the early '80s, the first clue of their existence came in 1970 when Leroy Stevens of the Jackson Laboratory in Bar Harbor, Maine, found strange looking cells in the embryos of mice that developed teratomas after birth.

Teratomas are growths that contain an odd assortment of tissue, including teeth, bone, skin and cartilage. Stevens called the cells that gave rise to teratomas "pluripotent embryonic stem cells," a name still in use today to describe the small number of cells in a fertilized egg that give rise to all the different organs and tissues of the body.

When an egg is fertilized by a sperm, it begins to divide. The first dividing cells are called totipotent, meaning that each one of them is capable of giving rise to all the cells in an organism, including the placenta, which supplies nutrition to a growing fetus through the umbilical cord. They are also called embryonic stem cells, and when they separate immediately after fertilization, they produce identical twins.

It is these cells that can produce a human being if implanted in the uterus of a women, and for that reason, congress has banned federal funding for human embryonic research. But scientists can use private funds for such research.

Early in cell division, cells lose their ability to create a placenta. These cells are called pluripotent because they still have the ability to make all other cell types in the body, but not a whole fetus.

Using private funds, James Thompson of the University of Wisconsin and John Gearhart of Johns Hopkins succeeded in isolating human pluripotent stem cells in 1998.

Later in fetal development, these cells become organ-specific stem cells that only make cells for a single organ. Or so it was thought. Now it seems that nature is a far more accommodating builder, making sure that stem cells from one organ could cross over to make cells from a different organ when needed.

"Stem cells seem to share properties," said Dr. Ronald McKay, a pioneer in stem cell research and chief of the molecular biology lab at the National Institute of Neurological Disorders and Stroke.

"You can go into blood and get heart and skeletal muscle. You can go into skeletal muscle and you can get blood or go into brain and get muscle," he said. "The potential to regenerate tissue is there and we have to find out how to use it."

A stem cells appears to heed the chemical signals from the environment in which it finds itself to turn on the appropriate genes that will then transform it into one of a potential variety of cells.

McKay's goal is to use brain stem cells to replace brain cells destroyed by Parkinson's disease or other neurological disorders. So far he and his colleagues have coaxed stem cells to make dopamine-producing neurons, the cells that die off in Parkinson's disease. Implanted into the brains of mice that mimic the symptoms of Parkinson's, the transformed cells restore function.

Wisconsin's Thompson has already used pluripotent stem cells to make human heart tissue, which he believes could have an immediate therapeutic benefit in repairing hearts damaged by heart disease. Animal research shows that transplanted healthy heart tissue integrates with the damaged heart and improves function.

The job of stem cells is to keep the body in a steady state of repair, at least until after the child-rearing period. They are busy regenerating the liver and replacing skin and intestinal cells and forming scar tissue. To a lesser degree they make brain, heart and muscle cells.

Yet, for all of their amazing qualities, stem cells are not perfect. They don't keep the brain or the body in perfect health.

"Those stem-cell mechanisms are not quite as powerful as we would like," said Dr. Dennis Choi of Washington University in St. Louis, who is using embryonic stem cells to reverse spinal cord injury in mice.

"Their potential is only now emerging, and that's because of our growing ability to manipulate these cells in recent years," he said.

"Our bodies are marvelous and have all kinds of protective mechanisms, but they can be helped to be better. We have an immune system that is designed to fight bacteria. But every once in a while, we do better when antibiotics give it a boost. What we're doing now is finding ways to boost our stem cells," Choi said.