Cellular conversion turns brain into blood.

Talk about a career change. The unspecialized cells that normally give rise to the various cell types in the brain can also act as bone marrow, the crucial source of an adult body's blood cells.

Scientists discovered this remarkable ability when they injected these so-called neural stem cells into the blood of mice whose own bone marrow had been almost completely destroyed by irradiation. The neural stem cells, whose progeny were identifiable by means of a genetic marker previously slipped into them, engrafted as normal bone marrow transplants do and began producing blood cells.

"We really had a hard time convincing ourselves of our own data," notes Angelo L. Vescovi of the National Neurological Institute in Milan, Italy. He, Christopher R.R. Bjornson of the University of Washington in Seattle, and their colleagues describe the neural stem cell transplants in the Jan. 22 SCIENCE.

The experiments suggest that a cell's lot in life, usually determined during the growth of an embryo, isn't as hard and fast as once thought. "Even when a cell seems to have committed to a particular organ, there are still some cells that can switch that fundamental identity. That's an intriguing biological concept," says Evan Y. Snyder of Children's Hospital in Boston, who has isolated human neural stems cells (SN: 11/7/98, p. 293).

Until recently, scientists assumed that most adult cells had made irreversible commitments to a particular fate, becoming heart cells or liver cells, for example. The cloning of Dolly the sheep and other animals from various adult cells challenged that dogma, however. Still, those experiments involved removing the genes of an adult cell and placing them into an egg, a transfer that somehow reverted the genes to their embryonic state (SN: 4/5/97, p. 214). In the new experiments, the researchers have shown that they can directly change the role of some adult cells simply by placing them in a new environment.

Vescovi notes that his unusual experiment was prompted in part by reports of brain tumors that contained muscle cells in addition to brain cells. Those cases hinted that brain cells could develop into very different cell types.

After injecting the neural stem cells into mice, the researchers showed that the cells seeded the animals' bone marrow and spleens, which also produce new blood cells. They also showed that individual white blood cells from the animals had the genetic marker belonging to the neural stem cells.

Although the researchers are confident that the transplanted neural stem cells produced new red blood cells, they haven't proved that point. Mature red blood cells have no DNA-containing nuclei, making it impossible for the investigators to detect the genetic marker used to label the neural stem cells and their progeny.

Vescovi's team is now testing whether human neural stem cells can also act as bone marrow when injected into mice. "If the principle holds for human cells, we'd like to try therapy," says Vescovi. Noting that hematopoietic stem cells, the bone marrow cells that give rise to blood, are difficult to grow and manipulate, the researcher suggests that neural stem cells might substitute for the treatment of many blood disorders.

"We have no problems expanding endless supplies of neural stem cells, and we even have human neural stem cells now," comments Snyder. "I'd be ecstatic if ... the cells I've isolated with one intent can now address a magnitude-greater level of diseases."

Neural stem cells may have a future outside the bloodstream as well. "We're actively investigating whether our [neural] stem cells can give rise to other solid organs. For instance, can they give rise to muscle or liver?" asks Snyder.

In addition to searching for the chemical cues that switch neural stem cells into blood producers, Vescovi plans to study whether hematopoietic stem cells or other nonneural tissues can give rise to brain cells.