Olfactory ensheathing cells promote proliferation and inhibit neuronal differentiation of neural progenitor cells through activation of Notch signaling

A population of neural progenitor cells (NPCs) has been known to exist in adult spinal cord and migrate toward the lesion regions during spinal cord injury (SCI). Although there are some positive effects of the transplanted olfactory ensheathing cells (OECs) on axonal regeneration in SCI, little is known about the effects and the underlying mechanism of these grafted OECs on NPCs. In this study, we have investigated how soluble factors derived from rat OECs regulate the proliferation and differentiation of rat NPCs. The conditioned medium from cultured OECs showed its ability to promote proliferation and inhibit neuronal differentiation of NPCs. Notch signaling was apparently involved in this process. With the addition of DAPT, which inhibited Notch signaling, the effects of OEC-conditioned medium on NPCs were blocked. We thus conclude that diffusible factors released from OECs activate the Notch signaling pathway to stimulate the proliferation and suppress neuronal differentiation of NPCs. These findings reveal the likely limitation of using OECs transplantation for SCI repair.