Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration
Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration
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间充质干细胞外泌体增强牙周膜细胞功能促进牙周组织再生
DOI：
10.1016/j.actbio.2019.03.021
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发表时间：
2019-04-15
影响因子：
9.7
通讯作者：
Toh, Wei Seong
中科院分区：
文献类型：
--
作者：
Chew, Jacob Ren Jie;Chuah, Shang Jiunn;Toh, Wei Seong
间充质干细胞（MSC）是治疗牙周缺陷的潜在疗法。人们越来越认识到间充质干细胞通过分泌营养因子（尤其是外泌体）介导组织修复。在这里，我们研究了装载人间充质干细胞外泌体的胶原海绵对免疫活性大鼠模型中手术造成的牙周骨内缺陷再生的治疗效果。我们观察到，与对照大鼠相比，外泌体治疗的大鼠通过牙周组织（包括新形成的骨和牙周韧带（PDL））的再生更有效地修复了缺陷。我们还观察到，随之而来的是细胞浸润和增殖的增加。因此，我们推测 MSC 外泌体通过增加细胞动员和增殖来增强再生。使用 PDL 细胞培养物，我们证明 MSC 外泌体可以通过 CD73 介导的腺苷受体激活促生存 AKT 和 ERK 信号来增加 PDL 细胞迁移和增殖。抑制 AKT 或 ERK 磷酸化可抑制 PDL 细胞迁移和增殖。我们的研究结果首次证明 MSC 外泌体可能通过增加 PDL 迁移和增殖来增强牙周再生。这项研究表明，间充质干细胞外泌体是一种可行的即用型、无细胞间充质干细胞疗法，可用于治疗牙周缺陷。意义声明间充质干细胞（MSC）疗法已证明具有治疗牙周缺陷的再生潜力。然而，从制造和储存到最终交付给患者的整个过程中，维持最佳细胞活力和活力的挑战阻碍了细胞疗法的转化。尽管使用 MSC 进行组织修复首先是基于其分化潜力，但 MSC 的治疗功效越来越多地归因于其旁分泌分泌，特别是外泌体或小细胞外囊泡。在这项研究中，加载MSC外泌体的胶原海绵增强了免疫活性大鼠牙周缺损模型中的牙周再生，且没有任何明显的副作用。这些发现为未来开发 MSC 外泌体作为牙周再生的无细胞策略奠定了基础。 (C) 2019 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Mesenchymal stem cells (MSCs) are potential therapeutics for the treatment of periodontal defects. It is increasingly accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly exosomes. Here, we investigated the therapeutic effects of human MSC exosome-loaded collagen sponge for regeneration of surgically created periodontal intrabony defects in an immunocompetent rat model. We observed that relative to control rats, exosome-treated rats repaired the defects more efficiently with regeneration of periodontal tissues including newly-formed bone and periodontal ligament (PDL). We also observed that concomitant with this, there was increased cellular infiltration and proliferation. We therefore postulated that MSC exosomes enhanced regeneration through increased cellular mobilisation and proliferation. Using PDL cell cultures, we demonstrated that MSC exosomes could increase PDL cell migration and proliferation through CD73-mediated adenosine receptor activation of pro-survival AKT and ERK signalling. Inhibition of AKT or ERK phosphorylation suppressed PDL cell migration and proliferation. Our findings demonstrated for the first time that MSC exosomes enhance periodontal regeneration possibly by increasing PDL migration and proliferation. This study suggests that MSC exosome is a viable ready-to-use and cell-free MSC therapeutic for the treatment of periodontal defects.Statement of significanceMesenchymal stem cell (MSC) therapies have demonstrated regenerative potential for the treatment of periodontal defects. However, translation of cellular therapies is hampered by challenges in maintaining optimal cell vitality and viability from manufacturing and storage to final delivery to patients. Although the use of MSCs for tissue repair was first predicated on their differentiation potential, the therapeutic efficacy of MSCs has increasingly been attributed to its paracrine secretion, particularly exosomes or small extracellular vesicles. In this study, MSC exosome-loaded collagen sponge enhanced periodontal regeneration in an immunocompetent rat periodontal defect model without any obvious adverse effects. These findings provide the basis for future development of MSC exosomes as a cell-free strategy for periodontal regeneration. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.