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。

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":"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。","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":"{\"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}","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

摘要

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。

查看原文本刊更多论文

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

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Journal of Oral Biosciences DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

4.40

自引率

12.50%

发文量

审稿时长

37 days