2. Academic Validation
  3. LARP7 enhances the potential of dental pulp stem cells to promote peripheral nerve repair

LARP7 enhances the potential of dental pulp stem cells to promote peripheral nerve repair

  • Stem Cells. 2026 May 23;44(6):sxag013. doi: 10.1093/stmcls/sxag013.
Zihan Yang 1,  Guanlin Qu 1,  Xiping Wang 2,  Li Wang 1 2,  Lu Chen 1,  Guiqiang Fu 3,  Wenze Chen 3,  Zitong Yang 4,  Wenjing Li 1,  Yuqiong Zhou 1,  Jiacheng Jin 5,  Linxi Zhou 6,  Duohong Zou 1
Affiliations

Affiliations

  • 1 Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200001, China.
  • 2 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, China.
  • 3 Stomatology Hospital and College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230000, China.
  • 4 Zhejiang Chinese Medical University School of Medical Technology and Information Engineering, Hangzhou, 310053, China.
  • 5 Touro College of Dental Medicine at New York Medical College, Hawthorne, NY 10532, USA.
  • 6 Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200001, China.
PMID: 41812059 DOI: 10.1093/stmcls/sxag013
Abstract

Background: Peripheral nerve injuries (PNIs) present a persistent clinical challenge due to 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.

Methods: DPSCs 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.

Results: LARP7 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 DPSCs differentiation into Schwann cell-like phenotypes.

Conclusions: Collectively, LARP7-mediated changes in DPSCs establish a new therapeutic paradigm that addresses the limitations of current stem cell-based interventions and enables the development of standardized biotherapeutics for peripheral nerve repair.

Keywords

mesenchymal stem cell; peripheral nerve injuries; regenerative medicine; stem cell therapy; tissue regeneration.

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