Homing In On Better Bone Marrow Transplants

Robert Sackstein (Harvard Medical School, Boston, MA) and colleagues report in the June 11 issue of The Journal of Cell Biology that a sugar-coated variant of a protein called CD44 acts as the homing molecule for human hematopoietic progenitor cells (HPCs). The HPCs normally reside in bone marrow, and serve as the source of all new blood cells. HPCs also circulate in the bloodstream. They find their way back to the bone marrow by attaching to a protein called E-selectin, which is made by cells that line the blood vessels. The same mechanism allows cells in bone marrow transplants to find their way to their correct place in the bone marrow, even after the cells have been injected directly into the bloodstream.

Sackstein and colleagues set out to find the protein from HPCs that attaches to E-selectin. They found that the CD44 variant allowed cells to roll across or attach to a layer of tethered, E-selectin-containing cells, even as a jet of water was acting to displace the cells.

The variant is made only by HPCs, and not by more mature blood cells. This restricted production of the variant should allow Sackstein to isolate HPCs before doing a bone marrow transplant, thus reducing the number of cells given to transplant recipients. A purer transplant would give clinicians greater control over the immune reaction to a transplant, perhaps reducing the likelihood of graft-versus-host disease.