Diffusible, membrane-bound, and extracellular matrix factors from olfactory ensheathing cells have different effects on the self-renewing and differentiating properties of neural stem cells

Transplantation of olfactory ensheathing cells (OECs) has been a promising strategy in enhancing central nervous system (CNS) regeneration. However, little is known about the effects of transplanted OECs on the self-renewal, neurogenesis, and oligodendrogenesis of neural stem cells (NSCs), which are known to play a very important role in the repair of damaged CNS tissue. In this study, we investigated the influence of diffusible, membrane-bound, and extracellular matrix factors from OECs on the self-renewal and differentiation properties of NSCs. We found that diffusible factors from cultured OECs promoted self-renewal, whereas the extracellular matrix molecules from OECs increased neurogenesis and oligodendrogenesis of NSCs. Furthermore, we demonstrated that directly coculturing OECs and NSCs inhibited not only self-renewal but also neurogenesis and oligodendrogenesis of NSCs. We propose three models for the interaction between transplanted OECs and endogenous NSCs. Our findings provide new insight into the ability of OECs to promote CNS repair and also indicate potential targets for manipulation of these cells to enhance their restorative ability.