State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Cell Prolif. 2021 Jul;54(7):e13074. doi: 10.1111/cpr.13074. Epub 2021 Jun 7.
Pulp regeneration brings big challenges for clinicians, and vascularization is considered as its determining factor. We previously accomplished pulp regeneration with autologous stem cells from deciduous teeth (SHED) aggregates implantation in teenager patients, however, the underlying mechanism needs to be clarified for regenerating pulp in adults. Serving as an important effector of mesenchymal stem cells (MSCs), exosomes have been reported to promote angiogenesis and tissue regeneration effectively. Here, we aimed to investigate the role of SHED aggregate-derived exosomes (SA-Exo) in the angiogenesis of pulp regeneration.
We extracted exosomes from SHED aggregates and utilized them in the pulp regeneration animal model. The pro-angiogenetic effects of SA-Exo on SHED and human umbilical vein endothelial cells (HUVECs) were evaluated. The related mechanisms were further investigated.
We firstly found that SA-Exo significantly improved pulp tissue regeneration and angiogenesis in vivo. Next, we found that SA-Exo promoted SHED endothelial differentiation and enhanced the angiogenic ability of HUVECs, as indicated by the in vitro tube formation assay. Mechanistically, miR-26a, which is enriched in SA-Exo, improved angiogenesis both in SHED and HUVECs via regulating TGF-β/SMAD2/3 signalling.
In summary, these data reveal that SA-Exo shuttled miR-26a promotes angiogenesis via TGF-β/SMAD2/3 signalling contributing to SHED aggregate-based pulp tissue regeneration. These novel insights into SA-Exo may facilitate the development of new strategies for pulp regeneration.
牙髓再生给临床医生带来了巨大的挑战，血管化被认为是其决定因素。我们之前曾在青少年患者中通过植入乳牙源性干细胞（SHED）聚集体实现了牙髓再生，但在成人中再生牙髓的潜在机制仍需阐明。外泌体作为间充质干细胞（MSCs）的重要效应器，已被报道能有效促进血管生成和组织再生。在此，我们旨在研究 SHED 聚集体衍生的外泌体（SA-Exo）在牙髓再生中血管生成的作用。
我们从 SHED 聚集体中提取外泌体，并将其用于牙髓再生动物模型。评估了 SA-Exo 对 SHED 和人脐静脉内皮细胞（HUVECs）的促血管生成作用。进一步研究了相关机制。
我们首先发现 SA-Exo 显著改善了体内牙髓组织再生和血管生成。接下来，我们发现 SA-Exo 促进了 SHED 的内皮分化，并增强了 HUVECs 的血管生成能力，这在体外管形成实验中得到了证实。机制上，富含于 SA-Exo 中的 miR-26a 通过调节 TGF-β/SMAD2/3 信号通路，在 SHED 和 HUVECs 中均改善了血管生成。
综上所述，这些数据表明，SA-Exo 转运的 miR-26a 通过 TGF-β/SMAD2/3 信号通路促进血管生成，有助于基于 SHED 聚集体的牙髓组织再生。这些关于 SA-Exo 的新见解可能有助于开发新的牙髓再生策略。
