Exploring the therapeutic potential of small extracellular vesicles derived from induced pluripotent stem cell in periodontal regeneration

IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences Pub Date : 2025-01-30 DOI:10.1016/j.job.2025.100621

Tingting Xu , Yi Peng , Yanan Xu , Jing Zhu , Qiao Yang , Yali Liu , Hefeng Yang

{"title":"Exploring the therapeutic potential of small extracellular vesicles derived from induced pluripotent stem cell in periodontal regeneration","authors":"Tingting Xu , Yi Peng , Yanan Xu , Jing Zhu , Qiao Yang , Yali Liu , Hefeng Yang","doi":"10.1016/j.job.2025.100621","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the role of small extracellular vesicles derived from induced pluripotent stem cells (iPSC-sEVs) in periodontal tissue regeneration, elucidate their potential molecular mechanisms, and provide theoretical guidance for the clinical application of iPSC-sEVs as a cell-free therapeutic strategy for periodontal tissue regeneration.</div></div><div><h3>Methods</h3><div>We investigated the effects of iPSC-sEVs on the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in vitro. The regenerative potential of iPSC-sEVs was evaluated in vivo, using a periodontal defect model. Bulk RNA sequencing was performed to elucidate the underlying molecular mechanisms.</div></div><div><h3>Results</h3><div>iPSC-sEVs were isolated, characterized, and systemically evaluated for regenerative potential. The results revealed that treatment with iPSC-sEVs significantly enhanced the proliferation, migration, and osteogenic differentiation of PDLSCs. In situ treatment with iPSC-sEVs loaded onto collagen sponges was performed in a rat model of periodontal defects. Micro-CT and histological analyses indicated that iPSC-sEV treatment markedly promoted alveolar bone repair and periodontal ligament regeneration. Mechanistically, the analysis of bulk RNA sequencing data coupled with experimental validation revealed that iPSC-sEV treatment significantly activated the mitogen-activated protein kinase (MAPK) signaling pathway in PDLSCs. Further investigation showed that the inhibition of this pathway completely abolished the proliferative effects of iPSC-sEVs on PDLSCs.</div></div><div><h3>Conclusions</h3><div>iPSC-sEVs promote PDLSC proliferation through MAPK signaling pathway activation, while also enhancing PDLSC migratory and osteogenic differentiation capacities, facilitates the repair and regeneration of damaged periodontal tissue and presents a potential novel therapeutic strategy for clinical periodontal tissue regeneration.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 1","pages":"Article 100621"},"PeriodicalIF":2.3000,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Oral Biosciences","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1349007925000106","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

To investigate the role of small extracellular vesicles derived from induced pluripotent stem cells (iPSC-sEVs) in periodontal tissue regeneration, elucidate their potential molecular mechanisms, and provide theoretical guidance for the clinical application of iPSC-sEVs as a cell-free therapeutic strategy for periodontal tissue regeneration.

Methods

We investigated the effects of iPSC-sEVs on the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in vitro. The regenerative potential of iPSC-sEVs was evaluated in vivo, using a periodontal defect model. Bulk RNA sequencing was performed to elucidate the underlying molecular mechanisms.

Results

iPSC-sEVs were isolated, characterized, and systemically evaluated for regenerative potential. The results revealed that treatment with iPSC-sEVs significantly enhanced the proliferation, migration, and osteogenic differentiation of PDLSCs. In situ treatment with iPSC-sEVs loaded onto collagen sponges was performed in a rat model of periodontal defects. Micro-CT and histological analyses indicated that iPSC-sEV treatment markedly promoted alveolar bone repair and periodontal ligament regeneration. Mechanistically, the analysis of bulk RNA sequencing data coupled with experimental validation revealed that iPSC-sEV treatment significantly activated the mitogen-activated protein kinase (MAPK) signaling pathway in PDLSCs. Further investigation showed that the inhibition of this pathway completely abolished the proliferative effects of iPSC-sEVs on PDLSCs.

Conclusions

iPSC-sEVs promote PDLSC proliferation through MAPK signaling pathway activation, while also enhancing PDLSC migratory and osteogenic differentiation capacities, facilitates the repair and regeneration of damaged periodontal tissue and presents a potential novel therapeutic strategy for clinical periodontal tissue regeneration.

查看原文本刊更多论文

探索由诱导多能干细胞衍生的细胞外小泡在牙周再生中的治疗潜力。

目的：探讨诱导多能干细胞（ipsc - sev）细胞外小泡在牙周组织再生中的作用，阐明其潜在的分子机制，为ipsc - sev作为牙周组织再生的无细胞治疗策略的临床应用提供理论指导。方法：体外研究ipsc - sev对牙周韧带干细胞（PDLSCs）增殖、迁移和成骨分化的影响。利用牙周缺损模型，对ipsc - sev的再生潜能进行体内评价。进行了大量RNA测序以阐明潜在的分子机制。结果：分离出ipsc - sev，对其进行了表征，并对其再生潜能进行了系统评估。结果显示，ipsc - sev显著增强了PDLSCs的增殖、迁移和成骨分化。在大鼠牙周缺损模型中，利用胶原海绵负载ipsc - sev进行原位治疗。显微ct和组织学分析表明，iPSC-sEV治疗显著促进牙槽骨修复和牙周韧带再生。在机制上，大量RNA测序数据分析结合实验验证表明，iPSC-sEV处理显著激活了PDLSCs中的丝裂原活化蛋白激酶（MAPK）信号通路。进一步的研究表明，抑制这一途径完全消除了ipsc - sev对PDLSCs的增殖作用。结论：ipsc - sev通过激活MAPK信号通路促进PDLSC增殖，同时增强PDLSC迁移和成骨分化能力，促进受损牙周组织的修复和再生，为临床牙周组织再生提供了一种潜在的新治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊