Functional differences and interactions between phenotypic subpopulations of olfactory ensheathing cells in promoting CNS axonal regeneration.

ABSTRACT

We demonstrate that there are significantly more p75 neurotrophin receptor- (NTR)-expressing cells in olfactory ensheathing cell (OEC) primary cultures from olfactory nerve rootlets (ONR), but a greater proportion of O4 antigen- and PSA-NCAM-expressing cells in parallel cultures from the nerve fibre layer of the olfactory bulb (OB). By co-culturing adult rat retinal ganglion cells (RGCs) with OECs derived from either ONR or OB tissue, we compared their neurite regrowth-promoting properties. In phenotypically unsorted cultures, there is greater RGC neurite regrowth on ONR OECs compared to OB OECs. Following immunoselection of ONR cells for p75 NTR, there is increased RGC neurite regrowth on the enriched population compared to the unselected cell population or the p75 NTR depleted population. When p75 NTR-enriched cells from ONR and OB cultures are compared directly, tissue source-related differences are no longer observed. Our previous work implicated a pertussis toxin (PTx)-sensitive G protein-linked signalling pathway in OEC regulation of neurite regrowth. We show that this pathway probably operates in interactions between the p75 NTR-positive and -negative cells; separated populations lose the PTx-mediated enhancement of neurite regrowth-promoting properties seen in mixed cultures. Optimum neurite regrowth is observed when both phenotypes are present in cultures from either ONR or OB, and where glial G-protein signalling is disabled by PTx before co-culture with neurons. We thus propose that p75 NTR-positive cells, whilst being the more effective neurite regrowth promoting subpopulation in isolation, cooperate with negative cells to provide optimum support for axonal regrowth.