The Role of Small Extracellular Vesicles Derived from Lipopolysaccharide-preconditioned Human Dental Pulp Stem Cells in Dental Pulp Regeneration
The Role of Small Extracellular Vesicles Derived from Lipopolysaccharide-preconditioned Human Dental Pulp Stem Cells in Dental Pulp Regeneration
复制标题
脂多糖预处理的人牙髓干细胞衍生的小细胞外囊泡在牙髓再生中的作用
DOI：
10.1016/j.joen.2021.03.010
复制
发表时间：
2021-05-24
影响因子：
4.2
通讯作者：
Chen, Wen-Xia
中科院分区：
文献类型：
--
作者：
Chen, Wen-Jin;Xie, Jing;Chen, Wen-Xia
前言：尽管目前再生牙髓治疗效果有限，但再生牙髓治疗技术已经在治疗模式上产生了可取的转变。间充质干细胞(MSCs)在温和的炎症环境中促进组织的再生和修复。MSCs来源的小细胞外小泡在MSCs调控的再生反应的旁分泌调节中起着至关重要的作用。然而，目前尚不清楚MSCs是否促进牙髓再生，或者这种促进作用是否由温和炎症环境中的SEV介导。本研究旨在阐明脂多糖(LPS)预适应的人牙髓干细胞(HDPSCs)来源的SEV对牙髓再生的影响。方法：从含或不含脂多糖的人DPSCs中分离出SEV，即N-SEV和L-SEV。体外观察N-SEV和L-SEV对大鼠骨髓间充质干细胞增殖、迁移、血管生成和分化的影响。将N-SEV或L-SEV植入大鼠无髓根管模型，移植30d后行苏木精-伊红染色、Masson染色和免疫组织化学染色。结果：N-SEV和L-SEV均能调节骨髓间充质干细胞的增殖、迁移、血管生成和分化。两种SEV都增强了体内再生组织的结构，更接近于正常牙髓的结构。L-SEV的效果比N-SEV更显著。结论：hDPSCs在温和的炎症微环境中释放的SEV能够促进牙髓再生，而不是瘢痕愈合，在再生牙髓治疗中具有潜在的应用前景。(J Endod 2021；47：961-969。)
Introduction: Regenerative endodontics has created a desirable shift in the treatment paradigm despite current limitations of regenerative outcomes. Mesenchymal stem cells (MSCs) facilitate tissue regeneration and repair in a mild inflammatory environment. Small extracellular vesicles (sEVs) derived from MSCs play an imperative role in the paracrine modulation of regenerative responses modulated by MSCs. However, it remains unknown whether MSCs enhance dental pulp regeneration or whether this enhancement is mediated by sEVs in a mild inflammatory environment. The present study aimed to elucidate the effects of sEVs originated from lipopolysaccharide (LPS)-preconditioned human dental pulp stem cells (hDPSCs) on dental pulp regeneration. Methods: All sEVs were isolated from hDPSCs cultured with or without LPS (ie, N-sEVs and L-sEVs, respectively). The effect of N-sEVs and L-sEVs on proliferation, migration, angiogenesis, and differentiation of rat bone marrow MSCs was identified in vitro. Moreover, N-sEVs or L-sEVs were implanted into rat pulpless root canal models, and the regenerated tissue in root canals was assessed via hematoxylin-eosin staining, Masson staining, and immunohistochemistry after 30 days of transplantation. Results: Both N-sEVs and L-sEVs could modulate BMSC proliferation, migration, angiogenesis, and differentiation. Both kinds of sEVs enhanced the structure of the regenerated tissue closer to that of a normal dental pulp in vivo. L-sEVs had a more significant effect than N-sEVs. Conclusions: sEVs released by hDPSCs in a mild inflammatory microenvironment are capable of facilitating the regeneration of dental pulp through functional healing instead of scar healing, which has potential applications in regenerative endodontics. (J Endod 2021;47:961-969.)