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源自人牙髓干细胞的凋亡细胞外囊泡促进牙周组织再生。

Apoptotic extracellular vesicles derived from human dental pulp stem cells facilitate periodontal tissue regeneration.

作者信息

Xia Junyi, Zhang Zeyu, Weng Jinlong, Zhu Guanxiong, Xu Zidan, Zeng Liting, Pathak Janak Lal, Yu Lina

机构信息

Department of Preventive Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, Guangdong, 510182, People's Republic of China.

出版信息

BMC Oral Health. 2025 Jul 11;25(1):1150. doi: 10.1186/s12903-025-06531-z.

DOI:10.1186/s12903-025-06531-z
PMID:40646544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12255120/
Abstract

OBJECTIVE

Apoptotic extracellular vesicles (ApoEVs) derived from human dental pulp stem cells (hDPSCs) are subcellular structures released during programmed cell death. These vesicles carry rich biological information and regulatory potential, and have demonstrated significance in regulating cell behavior and tissue repair. Human periodontal ligament stem cells (hPDLSCs) are key to regenerating periodontal tissue, and their osteogenic differentiation ability directly influences the repair and reconstruction of periodontal bone tissue. However, the potential of ApoEVs derived from human dental pulp stem cells (hDPSCs-ApoEVs) to regulate the osteogenic differentiation of hPDLSCs remains unexplored. This study aims to investigate the effects of hDPSCs-ApoEVs on the osteogenic differentiation of hPDLSCs, offering new insights and methods for treating periodontal bone tissue injuries, with important scientific and clinical implications.

METHODS

hDPSCs-ApoEVs were isolated via ultracentrifugation and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and Western blot. In vitro, hPDLSCs were treated with hDPSCs-ApoEVs to determine whether the vesicles could enter hPDLSCs and to assess the proliferation, migration, and osteogenic potential of hPDLSCs. In vivo, a rat periodontal bone defect model was established, with local injections of hDPSCs-ApoEVs or PBS administered every other day. After 6 weeks, the maxillae were collected and analyzed using micro-CT and histological staining.

RESULTS

In vitro, hDPSCs-ApoEVs promoted the migration and osteogenic differentiation of hPDLSCs. In vivo, treatment with hDPSCs-ApoEVs can enhance the recovery of periodontal bone defects in rats.

CONCLUSION

hDPSCs-ApoEVs play a significant role in promoting bone regeneration, suggesting their potential as a promising cell-free therapeutic strategy for periodontal bone tissue regeneration.

摘要

目的

源自人牙髓干细胞(hDPSCs)的凋亡细胞外囊泡(ApoEVs)是程序性细胞死亡过程中释放的亚细胞结构。这些囊泡携带丰富的生物学信息和调节潜能,已证明在调节细胞行为和组织修复方面具有重要意义。人牙周膜干细胞(hPDLSCs)是牙周组织再生的关键,其成骨分化能力直接影响牙周骨组织的修复与重建。然而,源自人牙髓干细胞的凋亡细胞外囊泡(hDPSCs-ApoEVs)调节hPDLSCs成骨分化的潜能尚未得到探索。本研究旨在探讨hDPSCs-ApoEVs对hPDLSCs成骨分化的影响,为治疗牙周骨组织损伤提供新的见解和方法,具有重要的科学和临床意义。

方法

通过超速离心分离hDPSCs-ApoEVs,并采用透射电子显微镜(TEM)、动态光散射(DLS)和蛋白质免疫印迹法进行表征。在体外,用hDPSCs-ApoEVs处理hPDLSCs,以确定囊泡是否能进入hPDLSCs,并评估hPDLSCs的增殖、迁移和成骨潜能。在体内,建立大鼠牙周骨缺损模型,每隔一天局部注射hDPSCs-ApoEVs或PBS。6周后,收集上颌骨并使用显微CT和组织学染色进行分析。

结果

在体外,hDPSCs-ApoEVs促进了hPDLSCs的迁移和成骨分化。在体内,hDPSCs-ApoEVs治疗可增强大鼠牙周骨缺损的恢复。

结论

hDPSCs-ApoEVs在促进骨再生中发挥重要作用,表明其作为牙周骨组织再生的一种有前景的无细胞治疗策略的潜力。

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本文引用的文献

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Extracellular vesicles from apoptotic BMSCs ameliorate osteoporosis via transporting regenerative signals.凋亡骨髓间充质干细胞来源的细胞外囊泡通过传递再生信号改善骨质疏松症。
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Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells.
牙髓和牙周韧带干细胞的单细胞转录组分析。
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CGRP-Loaded Porous Microspheres Protect BMSCs for Alveolar Bone Regeneration in the Periodontitis Microenvironment.载降钙素基因相关肽多孔微球在牙周炎微环境中保护骨髓间充质干细胞用于牙槽骨再生。
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Mesenchymal Stem Cells-Derived Apoptotic Extracellular Vesicles (ApoEVs): Mechanism and Application in Tissue Regeneration.间质干细胞衍生凋亡细胞外囊泡(ApoEVs):在组织再生中的机制与应用。
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Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells.大麻二酚挽救 TNF-α 抑制的牙髓干细胞增殖、迁移和成骨/成牙分化。
Biomolecules. 2023 Jan 6;13(1):118. doi: 10.3390/biom13010118.
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Apoptotic extracellular vesicles alleviate Pg-LPS induced inflammatory responses of macrophages via AMPK/SIRT1/NF-κB pathway and inhibit osteoclast formation.凋亡细胞外囊泡通过 AMPK/SIRT1/NF-κB 通路减轻 Pg-LPS 诱导的巨噬细胞炎症反应,并抑制破骨细胞形成。
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