Abstract

BackgroundPeripheral nerve injuries (PNIs) present a persistent clinical challenge because of the intrinsically limited regenerative capacity of peripheral nerves. While dental pulp stem cells (DPSCs) exhibit significant neuroregenerative potential, their therapeutic efficacy is constrained by hostile microenvironments and inherent functional heterogeneity. Genetic modification may offer a promising strategy to enhance their therapeutic capabilities.MethodsDPSCs were induced toward neural lineage differentiation, and key gene candidates were identified through qRT-PCR. Lentiviral-mediated gene interference was performed to modulate target gene expression, followed by comprehensive analysis of differentiation outcomes using qRT-PCR, Western blotting, and immunofluorescence assays. RNA sequencing was employed to uncover associated signaling pathways, which were subsequently validated through pharmacological inhibition with specific inhibitors. The therapeutic efficacy of genetically engineered DPSCs was evaluated in a rat model of sciatic nerve crush injury, with neural regeneration quantitatively assessed via neuroelectrophysiological measurements and histological analyses.ResultsLARP7 positively regulated the Schwann cell-like differentiation of DPSCs, as well as their trophic and anti-inflammatory effects, thus enhancing its therapeutic effects on nerve repair and promoting functional recovery. Mechanistically, we found that LARP7 remodeled cytokine-cytokine receptor interactions, enhancing trophic support while attenuating proinflammatory responses, and activated the PI3K-Akt-mTOR signaling pathway, with ERBB4 serving as a critical downstream effector, promoting DPSC differentiation into Schwann cell-like phenotypes.ConclusionsCollectively, LARP7-mediated changes in DPSCs establish a new therapeutic paradigm that addresses the limitations of current stem cell-based