wo papers in the current hot list prove that work on stem cells is still alive and well in the United States, despite recent political decisions and the well-publicized departures of some researchers. Diane Krause, of Yale University School of Medicine, and Neil Theise, of New York University Medical School, led a team that proved that a single omnipotent cell stem could completely repopulate the bone marrow of a recipient. Piero Anversa’s group at New York Medical College showed that bone marrow cells could regenerate the heart muscle damaged in a heart attack.

Krause and Theise (#10) focused on hematopoietic stem cells (HSCs), the cells, normally resident in bone marrow, that give rise to components of the blood system. The researchers had already shown that adult HSCs are surprisingly adaptable; for example, they can differentiate into mature liver cells, in mouse and human. In other cases, bone marrow cells turn into skeletal muscle cells or the glial cells that support nerve cells in the brain. These transformations upset a fundamental precept of anatomy, that the three layers into which an embryo differentiates—the ectoderm, mesoderm, and endoderm—are fixed. Liver is endodermal. Glial cells are ectodermal. Bone marrow, being mesodermal, should not be able to turn into either of them.

While Krause and Theise knew that bone marrow cells could break the rules, they did not know which particular cells were capable of doing so. HSCs are extremely rare—fewer than 1 in 10,000 bone marrow cells—and do not seem to have any obvious markers on the cell surface by which they could be identified. A very few HSCs, between 1 and 10, injected into a mouse whose own bone marrow cells have been killed, are capable of finding their way to the bone marrow and repopulating it permanently. Krause and Theise used the homing ability of these cells to concentrate and purify them.

They injected irradiated female mice with donor marrow cells from a male, enriched for hematopoietic stem cells as far as possible and labelled with a dye. Two days later, they separated out the dyed cells from the recipient’s marrow, and injected a single cell into each of a second group of 30 irradiated females. Five mice treated in this way survived for almost a year. By contrast, if irradiated females were simply given 1,000 or 100 enriched bone marrow cells that had not first gone through the homing procedure, none of them survived long. So the homing procedure concentrates the HSCs considerably.

Looking in detail at the cells of the recipients, the group found descendants of the transplanted cell in several places, including the epithelial cells of the digestive system, the liver, the lungs, and the skin. The work has several implications for medicine. One of the more provocative is that these cells could be used for genetic therapy. They are reasonably easy to engineer, and could, for example, repopulate the lungs of cystic fibrosis sufferers with cells that do not have the cystic fibrosis defects. That, however, is probably some way off. Piero Anversa’s approach (#6) could find almost immediate applications.

Anversa’s group also enriched bone marrow cells and then injected the cells into the heart muscle after simulating a heart attack by cutting off the blood supply to the heart. Within 10 days, more than two-thirds of the damaged heart muscle was occupied by growing muscle cells and blood vessels derived from the injected bone marrow cells. In the normal aftermath of a heart attack, the muscle cells die and are replaced by scar tissue, which severely limits the performance of the heart. For that reason experimenters have tried transplanting a wide range of cell types into damaged heart, with limited and variable success. Anversa’s group showed that bone marrow cells seem to work. If the cells can prevent scar tissue forming, they might be able to stop the progression from heart attack to heart failure. With improved enrichment techniques, and the possibility of taking cells quickly from the patient’s own bone marrow, treatment of heart attacks could be revolutionized.