January 27, 2006

Study identifies molecule essential for proper localization of blood stem cells

Scientists at the MGH Center for Regenerative Medicine (CRM) have defined a molecule that dictates how blood stem cells travel to the bone marrow and establish blood and immune cell production. The discovery in an animal model may help improve bone marrow transplantation and the treatment of several blood disorders.

"This is another remarkable example of how bone and bone marrow interact. A receptor known to participate in the body's regulation of calcium and bone also is critical for stem cells to engraft in the bone marrow and regenerate blood and immune cells," says David Scadden, MD, director of the MGH-CRM. "It reminds us how looking closely at where stem cells reside may tell us a lot about how to manipulate them," Scadden is senior author of the report, which will be published in the journal Nature and is available online.

Hematopoietic or blood stem cells are critical to the daily production of more than 10 billion blood cells and are the basis for bone marrow transplant therapy for cancer. These cells are extremely powerful at regenerating blood and immune cells, but only if they travel to the proper location when introduced into the body, a process that depends on largely unknown molecules. Investigating evidence that suggested fundamental interactions between the processes of bone formation and stem cell development, the researchers found that a molecule called the calcium-sensing receptor appears to direct stem cells to the marrow via its interaction with the bone protein collagen I.

"Since there already are drugs available that target this receptor, we may be able to quickly adapt these findings in animals to the treatment of human patients," says Scadden. MGH co-authors of the study are Gregor Adams, PhD; Karissa Chabner; Ian Alley; Douglas Olson; Zbigniew Szczpiorkowski, MD; and Mark Poznansky, MD, PhD — all of the CRM.