New ingredient completes marrow recipe.

In bone marrow, where blood cells are born, a few cells have the unique ability to develop into any type of blood cell, as needed, and to produce offspring that can do the same.

After years of experiments failing to reveal what maintains this remarkable population of self-perpetuating cells, called hematopoietic stem cells, researchers working with mice have now discovered a way to propagate the cells in the laboratory. If the method works for human blood cells, it would likely be a windfall for the treatment of cancer and genetic disorders.

Scientists have established that in order to thrive and multiply, stem cells need the support of two other types of cells found in bone marrow: marrow fibroblasts and endothelial cells. In the laboratory, however, the presence of these support cells is not enough to keep a culture of stem cells from dying off within a few weeks. Instead of spawning more of their own kind during that time, the stem cells give rise only to ordinary, mortal blood cells.

Researchers have now discovered the need for a third crucial ingredient, a chemical messenger called thrombopoietin. "We're just completely mind-boggled," says study coauthor Stephen H. Bartelmez of the Seattle Biomedical Research Institute. "No one has ever guessed that this was what was going on."

When the researchers added thrombopoietin to samples of bone marrow that contained blood stem cells and the support cells, the stem cells survived and reproduced for 4 months, they report in the July 6 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. The group has now maintained a population of living stem cells in the laboratory for 9 months.

The team transplanted some of the cultured cells into mice whose own blood cells the scientists had killed by radiation. Without the ability to make blood, the mice would die rapidly. After the transplants, however, the mice have now survived for more than a year.

Although thrombopoietin appears to act directly by binding to receptors on the stem cells, Bartelmez says the most important action may be indirect. Thrombopoietin seems to signal the growth of cells called megakaryocytes, which help direct stem-cell production.

"We have finally determined the microenvironment that stem cells live in inside the body and have recreated that outside of the body," Bartelmez says. "We have great hopes that this will work in humans because we now know that we were missing an entire cell type before."

If physicians can also control human stem-cell growth, it may aid cancer patients whose blood cells are obliterated by radiation or chemotherapy. The ability to grow blood stem cells may also help scientists treat genetic disorders by replacing patients' stem cells with cells that contain engineered genes.

E. Richard Stanley of the Albert Einstein College of Medicine in New York City comments that the new method's relative simplicity suggests that researchers may easily translate it to human cells.

Darwin J. Prockop of MCP Hahnemann University in Philadelphia, however, is more doubtful. "It's a long way away from saying you could do the same thing in humans," he cautions. "There are a lot of important differences between mice and people."