HARVARD GAZETTE ARCHIVES

Experiments in mice revealed that the placenta harbors a large supply of hematopoietic (blood-forming) stem cells. These cells, which appear very early in development, are able to generate more blood stem cells and can give rise to a complete blood system when transplanted into an adult. Unlike other sites where blood stem cells are found during embryonic development, such as the liver, the stem cells in the placenta can increase in number without giving rise to mature, specialized cells.

"There must be something unique about the placenta that nurtures blood stem cells and discourages them from differentiating," says Stuart Orkin, a Howard Hughes Medical Institute investigator at Children's and DFCI, and a senior investigator of the study. "If we figure out what's special about the placental environment, we may learn how to grow blood stem cells in large numbers for clinical application."

Blood stem cells are used in treating blood cancers like leukemia and other blood diseases, and in patients receiving transplants, but growing them in quantity is difficult. The cells don't multiply readily in the laboratory, so they must be harvested from bone marrow by needle aspiration, a painful procedure, or coaxed into the blood and then collected. Both methods yield only a limited number of blood stem cells.

For more than a decade, scientists have believed that blood stem cells are made only in the embryo itself, within the region of the developing aorta. No role was suspected for the placenta, which has been seen as simply a place for nutrient exchange and waste removal between mother and fetus. But rather than merely providing nutrients, Orkin says, the placenta may also provide an "infusion" of blood stem cells to the fetus.

"This research reveals a new organ for blood development," says Orkin, who is also the David G. Nathan Professor of Pediatrics at Harvard Medical School. "It is surprising that this role for the placenta has been overlooked for so many years."

The study, published in the March issue of the journal Developmental Cell, found that blood stem cells appeared in the placenta early, with numbers peaking mid-gestation. Only the fetal liver, where blood stem cells are known to expand tremendously, had greater numbers of blood stem cells.