State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, China.
School of Medicine, University of Electronic Science and Technology of China, China.
Acta Biomater. 2022 Mar 1;140:610-624. doi: 10.1016/j.actbio.2021.11.039. Epub 2021 Nov 28.
The dental pulp is critical for physiological vitality of the tooth, and dental pulp regeneration has great potential for rebuilding live pulp tissue after pulp disease. Schwann cells (SCs) play a critical role in the support, maintenance, and regeneration of nerve fibers in dental pulp. Extracellular vesicles (EVs), which possess cell homing and tissue repair potential, derived from SCs (SC-EVs), can regulate dental mesenchymal stem cells (MSCs) proliferation, multipotency, and self-renewal. However, the role of SC-EVs in dental pulp tissue regeneration remains unclear. To address this question, we treated dental pulp stem cells (DPSCs) and bone marrow stem cells (BMSCs) with SC-EVs, and the results showed an obvious increase in the proliferation, migration, and osteogenic differentiation of both cell types. SC-EVs also promoted neurite outgrowth and neuron migration of rat dorsal root ganglia, as well as vessel formation in vitro. In an in vivo model of subcutaneous, SC-EVs enhanced the recruitment of endogenous vascular endothelioid-like cells and MSCs, and promoted the formation of a pulpo-dentinal complex-like structure. Finally, mass spectrometry analyses and western blot revealed that stromal cell-derived factor 1 (SDF-1, also known as CXCL12) plays a dominant role in SC-EVs. Together, these data suggest that SC-EVs successfully recruit endogenous stem cells to promote dental pulp regeneration. Our results provide a cell-free strategy for pulp regeneration that avoids the risks associated with stem cell transplantation. STATEMENT OF SIGNIFICANCE: Dental pulp is vulnerable to infections resulting from dental care, trauma, and multiple restorations, with such infections resulting in pulpitis and pulp necrosis. The current endodontic treatment of irreversible pulp disease cannot restore the function of dental pulp and tissue engineering strategies using cell-based approaches are limited by several disadvantages, including immune rejection and limited cell sources. In this study, we found that schwann cells-derived EVs facilitated dental pulp regeneration through endogenous stem cells recruitment via SDF-1/CXCR4 axis without exogenous cell transplantation. We believe that our study makes a significant contribution to describe a cell-free strategy to promote dental pulp regeneration.
牙髓对于牙齿的生理活力至关重要，牙髓再生具有在牙髓疾病后重建活牙髓组织的巨大潜力。许旺细胞（SCs）在牙髓中神经纤维的支持、维持和再生中发挥着关键作用。来源于许旺细胞的细胞外囊泡（EVs）具有细胞归巢和组织修复的潜力，可调节牙髓间充质干细胞（MSCs）的增殖、多能性和自我更新。然而，SCs-EVs 在牙髓组织再生中的作用尚不清楚。为了解决这个问题，我们用 SC-EVs 处理牙髓干细胞（DPSCs）和骨髓基质干细胞（BMSCs），结果显示这两种细胞类型的增殖、迁移和成骨分化明显增加。SCs-EVs 还促进了大鼠背根神经节的轴突生长和神经元迁移，以及体外血管形成。在皮下的体内模型中，SCs-EVs 增强了内源性血管内皮样细胞和 MSCs 的募集，并促进了牙髓-牙本质复合体样结构的形成。最后，质谱分析和 Western blot 显示基质细胞衍生因子 1（SDF-1，也称为 CXCL12）在 SC-EVs 中起主导作用。综上所述，这些数据表明 SC-EVs 成功招募内源性干细胞促进牙髓再生。我们的研究结果为避免与干细胞移植相关风险的牙髓再生提供了一种无细胞策略。
牙髓容易受到牙科护理、创伤和多次修复的感染，这些感染会导致牙髓炎和牙髓坏死。目前不可逆性牙髓病的牙髓治疗不能恢复牙髓的功能，基于细胞的组织工程策略受到多种缺点的限制，包括免疫排斥和有限的细胞来源。在这项研究中，我们发现许旺细胞衍生的 EVs 通过 SDF-1/CXCR4 轴促进牙髓再生，无需外源性细胞移植，通过招募内源性干细胞。我们相信我们的研究对描述一种无细胞策略来促进牙髓再生做出了重要贡献。
