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People who have had radiation or chemotherapy tend to have an accumulation of fat cells in their bone marrow. Now, Children’s researchers have found that this fatty infiltration isn’t benign: It actually inhibits the marrow’s blood-forming activity, impeding patients’ recovery from marrow and cord-blood transplants.
The researchers, led by George Daley, MD, PhD, director of Children’s Stem Cell Transplantation Program, and Olaia Naveiras, MD, PhD, of the Division of Pediatric Hematology/Oncology, first showed, in mice, that marrow from the fattier parts of the skeleton have far fewer blood stem cells and progenitor cells. In a culture dish, the mere presence of fat cells, or adipocytes, was enough to slow the proliferation of blood-forming cells.
"This contradicts the classical dogma that bone marrow adipocytes are merely space fillers," says Daley. "Rather, they make it harder to recover from chemotherapy or radiation because they actively suppress blood production. If we could prevent adipocytes from invading the bone marrow, patients might be able to recover faster."
Mice that were treated with a compound that inhibits fat formation, or that were genetically incapable of forming fat cells, were quicker to build up their bone marrow after it was depleted by irradiation. Since several adipocyte inhibitors are already in clinical testing for obesity, and Daley and Naveiras hope that one of these could help people recover faster from marrow and cord-blood transplants.
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