Dental pulp stem cells alleviate Schwann cell pyroptosis via mitochondrial transfer to enhance facial nerve regeneration

Bibliographic Details
Title: Dental pulp stem cells alleviate Schwann cell pyroptosis via mitochondrial transfer to enhance facial nerve regeneration
Authors: Xiaoyu Zheng, Juan Wang, Heng Zhou, Ying Chai, Ziwei Li, Minjie Chen, Zihan Yang, Chun Xu, Chang Lei, Yan He, Duohong Zou, Qingsong Ye
Source: Bioactive Materials, Vol 47, Iss , Pp 313-326 (2025)
Publisher Information: KeAi Communications Co., Ltd., 2025.
Publication Year: 2025
Collection: LCC:Materials of engineering and construction. Mechanics of materials
LCC:Biology (General)
Subject Terms: Dental pulp stem cells, Mitochondrial transfer, Facial nerve regeneration, Materials of engineering and construction. Mechanics of materials, TA401-492, Biology (General), QH301-705.5
More Details: Dental pulp stem cells (DPSCs) have demonstrated remarkable potential in enhancing peripheral nerve regeneration, though the precise mechanisms remain largely unknown. This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer. In a crab-eating macaque model, we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration, facilitating tissue proliferation and myelin recovery. We further established a rat facial nerve injury (FNI) model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells. A pivotal mitochondrial protective mechanism, resembling the effects of a ROS-targeted inhibitor, involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes, while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects. TNFα secreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs, enhancing mitochondrial transfer and adaptive stress responses, thereby promoting mitochondrial protection against pyroptosis in Schwann cells, as reflected in the improved therapeutic efficacy of TNFα-preconditioned DPSCs in the FNI model. These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer, presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2452-199X
Relation: http://www.sciencedirect.com/science/article/pii/S2452199X25000398; https://doaj.org/toc/2452-199X
DOI: 10.1016/j.bioactmat.2025.01.031
Access URL: https://doaj.org/article/750cab3cfb1748f9a90797064e8cab49
Accession Number: edsdoj.750cab3cfb1748f9a90797064e8cab49
Database: Directory of Open Access Journals
More Details
ISSN:2452199X
DOI:10.1016/j.bioactmat.2025.01.031
Published in:Bioactive Materials
Language:English