The finding could be critical for possible stem cell treatments for the myelinating disease multiple sclerosis. “The problem [with stem cell treatments] is not getting the stem cells; the problem is getting the cells to differentiate at the right stage,” says Fields. Adenosine looks like a promising stop signal for OPCs. And, as a further enticement, Fields showed that a brief exposure to adenosine might be enough to set cells on the right path.
Fields added a wide variety of biomolecules to OPCs and found that adenosine alone could reduce proliferation and induce everything from differentiation markers to a differentiated morphology and myelination. Adenosine receptor antagonists, meanwhile, prevented the changes in OPC proliferation and morphology normally caused by active neurons.
These results contrasted with the group's earlier findings with Schwann cells, which provide myelination for the peripheral nervous system (PNS). For Schwann cells it is ATP that is active but with an opposite effect: the ATP arrests maturation. This may give the PNS axons time to mature before they are surrounded by myelin.
The regulation of the two systems will take some time to decipher. ATP and adenosine not only have different effects on OPCs and Schwann cells, but one metabolite can be converted to the other via extracellular enzymes. Fields thinks the decoding effort will be worthwhile. “As neuroscientists we are all focused on rapid communication,” he says, “but all cells communicate, and this is one of the most ancient systems.” ▪