Sympathy for stem cells

JCB • VOLUME 172 • NUMBER 5 • 2006 640 T he sympathetic nervous system prepares the body for emergencies. Heart rate and blood pressure rise, pupils dilate, blood is shunted from skin to muscle, and the gut shuts down. Now, Yoshio Katayama, Paul Frenette (Mount Sinai School of Medicine, New York, NY), and colleagues suggest another consequence of sympathetic nervous system activation: hematopoietic stem and progenitor cells (HSPCs) exit the bone marrow and enter the blood. These HSPCs may be anticipating future injuries that will need a repair crew. Frenette started out not with the nervous system but with a sulfated sugar polymer from seaweed. This sugar could mobilize HSPCs, presumably via an effect on adhesion, and the mouse Cgt enzyme made a sulfated glycolipid that looked similar. Mice lacking this Cgt enzyme had impaired HSPC mobilization. But ideas about adhesion problems fell away as the team realized that the mutant mice had other problems. The mice have severe defects in their sympathetic nervous system because they cannot make major myelin sheath components. Chemical poisoning of the sympathetic nervous system also led to defects in HSPC mobilization in wild-type mice. The team found that the sympathetic nervous system works cooperatively with the cytokine G-CSF to change the morphology and behavior of osteoblasts. These bone-generating cells normally make the CXCL12 chemokine, which attracts HSPCs to keep them in the bone marrow. But the G-CSF and sympathetic nervous system signals reduced CXCL12 levels so that HSPCs could escape into the bloodstream. Enforced mobilization is used clinically to harvest HSPCs, but the physiological signifi cance of the mobilization, and the uses to which these mobilized cells are put, are poorly defi ned. One report suggests that running a marathon gets HSPCs out, perhaps to do repairs. Frenette plans to test conditions such as these, and to determine what cell type the G-CSF is acting upon.