ABSTRACT Limited regeneration of central nervous system (CNS) axons is a major barrier to recovery after CNS injury. Major advances have been made in identifying neuron-intrinsic mechanisms to promote axonal growth, but regenerating axons still require an environment that is growth-permissive. Although the astroglial scar has been considered to be a major inhibitory barrier to axon regeneration, there is mounting evidence that in certain conditions, reactive astrocytes may aid, rather than inhibit, regeneration of axons across the injury site. One possible explanation that might reconcile these conflicting roles of the astroglial scar is that there are astrocyte subpopulations that can inhibit, and other subpopulations that can permit, axon regeneration. One potential source of these regeneration-permissive astrocytes is oligodendrocyte progenitor cells (OPCs), which we and others have shown can differentiate into astrocytes after spinal cord injury (SCI). Since this differentiation capacity is limited to about 10-20% of OPCs in the glial scar region, we hypothesize that enhancing the number of OPC-derived astrocytes can enhance axon regeneration by increasing the amount of regeneration-permissive substrate across the injured spinal cord.