To test the idea, the researchers examined mice lacking the enzyme responsible for making sulfatide.
"Lo and behold, mice lacking the enzyme Cgt did not mobilize hematopoietic stem cells at all when treated with the stimulating factor G-CSF or fucoidan," Dr. Frenette said. "You don't get such dramatic results that often in science. We knew we had stumbled onto something important."
To their surprise, further study failed to connect the stalled stem cell movement to sulfatide. Rather, they found, the deficiency stemmed from a defect in the transmission of signals sent via the sympathetic nervous system. The products of Cgt contribute to the myelin sheath that coats and protects nerve cells, they explained.
Mice with other nervous system defects also exhibited a failure to mobilize bone marrow stem cells, they found. Moreover, drugs that stimulate the sympathetic nervous system restored stem cell movement into the blood stream in mice with an impaired ability to respond to norepinephrine, the signature chemical messenger of the sympathetic system.
"The nervous system plays an important role in producing signals that maintain the stem cell niche and retention in bone marrow," Dr. Frenette said.
"The new findings add another dimension of complexity to the processes involved in stem cell maintenance and mobilization and emphasize the interrelationships among the nervous, skeletal and hematopoietic systems," he added. "They all have to work together to talk to each other to produce blood and maintain stem cells."
The results suggest that differences in the sympathetic nervous systems of stem cell donors may explain "conspicuous variability" in the efficiency with which they mobilize hematopoietic cells into the bloodstream, the researchers said. Furthermore, drugs that alter the signals transmitted by the sympathetic nervous system to the stem cells in bone may offer a novel
'"/>
Contact: Mount Sinai Press Office
newsmedia@mssm.edu
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine
26-Jan-2006