Co-culture of human umbilical vein endothelial cells with dental pulp-derived mesenchymal stem cells enhance the migration and differentiation potential to neural progenitor like cells

Abstract

Regeneration of peripheral nerve injury remains difficult to achieve with fully functional recovery in clinical settings. Recently, stem cell transplantation for peripheral nerve regeneration has been proposed as a potential strategy. In this study, we investigated whether human dental pulp-derived mesenchymal stem cells (DP-MSCs) could be induced into neural progenitor cells (NPCs). In the neurovascular niche, neuron cells and vascular endothelial cells closely influence each other, and various factors secreted by vascular endothelial cells can improve the survival rate and axonal growth of neurons. To mimic this niche, human umbilical vein endothelial cells (HUVECs) were cocultured with DP-MSCs and induced to differentiate into NPCs. After coculture with HUVECs, the differentiated NPCs derived from DP-MSCs showed increased expression of migration-related genes (VCAM, ALCAM, and E-cadherin) and NPC-specific markers (Nestin, Msi1, PAX6, and SOX2). Further, we investigated their therapeutic effect in a rat sciatic nerve crush model. After the crush injury, we locally transplanted two types of NPCs induced from DP-MSCs: differentiated NPCs cocultured with HUVECs (HUVEC–NPC) and those induced without HUVECs (di-NPC). The HUVEC–NPC group showed better functional recovery of the five-toe spreading reflex compared with the di-NPC group. In addition, gait angle analysis showed that transplantation of HUVEC–NPC supported the recovery of normal ankle joint angles during the mid-stance and toe-off phase at 2 weeks after injury. Our findings suggest that NPCs induced from DP-MSCs cocultured with HUVECs may be potential therapeutic agents for sciatic nerve injury.