Olfactory Ensheathing Cells Promote Differentiation of Neural Stem Cells and Robust Neurite Extension

Abstract

Aims The goal of this study was to gain insight into the signaling between olfactory ensheathing cells (OECs) and neural stem cells (NSCs). We sought to understand the impact of OECs on NSC differentiation and neurite extension and to begin to elucidate the factors involved in these interactions to provide new targets for therapeutic interventions. Materials and Methods We utilized lines of OECs that have been extremely well characterized in vitro and in vivo along with well studied NSCs in gels to determine the impact of the coculture in three dimensions. To further elucidate the signaling, we used conditioned media from the OECs as well as fractioned components on NSCs to determine the molecular weight range of the soluble factors that was most responsible for the NSC behavior. Results We found that the coculture of NSCs and OECs led to robust NSC differentiation and extremely long neural processes not usually seen with NSCs in three dimensional gels in vitro. Through culture of NSCs with fractioned OEC media, we determined that molecules larger than 30 kDa have the greatest impact on the NSC behavior. Conclusions Overall, our findings suggest that cocultures of NSCs and OECs may be a novel combination therapy for neural injuries including spinal cord injury (SCI). Furthermore, we have identified a class of molecules which plays a substantial role in the behavior that provides new targets for investigating pharmacological therapies.

Co-Transplantation of Adipose Tissue-Derived Stromal Cells and Olfactory Ensheathing Cells for Spinal Cord Injury Repair

“…Another example of contact mediated increase of axonal outgrowth induced by OECs includes DRG axons grown on myelin substrates [44]. In our study, the secretome of OECs did not reveal to be a growth promoting substrate for axonal outgrowth of DRG explants, even though there is a substantial body of literature supporting the relevance of OECs' secreted factors in axonal regeneration context [45][46][47]. The contact-mediated ability of OECs might be partially due to the action of metalloproteinases (MMPs) such as MMP-2, MMP-3, and MT1-MMP, which seem to play a role on cellular motility and on their neurotrophic properties [48].…”

Rostro‐caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites

“…It is known that in the CNS, the effects of glial cells on neuronal development differ according to their phenotype (Powell et al ., ; Rakic, ). Similarly, in the main olfactory system, in vitro and in vivo data from several studies have indicated that OEC can act differently in neuronal development according to their phenotypes (Kafitz & Greer, ; Wewetzer et al ., ; Lipson et al ., ; Zhang et al ., ; Su & He, ; Jiao et al ., ; Sethi et al ., ). Mature OECs expressing the neurotrophin receptor p75 NTR have been shown to increase neurite outgrowth significantly in brain slices (Jiao et al ., ).…”

Adult stem cells in neural repair: Current options, limitations and perspectives

“…They also aid in tissue repair by effecting structural remodeling and support, modulating the immune system, enhancing neurotrophic and antigenic stimuli and metabolizing toxic macromolecules. Finally, OECs may be transplanted together with growth factor (e.g., bFGF, or basic fibroblast growth factor) to sustain cell survival and proliferation [39][40][41] .…”