Pulp-Derived Exosomes in a Fibrin-Based Regenerative Root Filling Material
Pulp-Derived Exosomes in a Fibrin-Based Regenerative Root Filling Material
复制标题
DOI：
10.3390/jcm9020491
复制
发表时间：
2020-02-01
影响因子：
3.9
通讯作者：
Weber, Franz E.
中科院分区：
文献类型：
--
作者：
Ivica, Anja;Ghayor, Chafik;Weber, Franz E.
再生牙髓学被描述为牙科的一种范式转变，尽管它目前仅限于未成熟的牙齿和修复而不是再生的结果。由于监管问题，无细胞治疗受到青睐。然而，将宿主来源的干细胞招募到所需部位仍然具有挑战性。我们调查了牙髓来源的外体，它是含有蛋白质、脂类、RNA和DNA的细胞外小泡，因此反映了它们的亲代细胞，是否可以用于这一目的。使用外切体可能比直接使用移植的干细胞具有明显的优势，因为它具有更高的安全性，更容易分离、保存和处理。在这里，我们从培养的第三磨牙牙髓细胞中获取外切体，并通过透射电子显微镜和Western blotting对其进行评估。将人间充质干细胞(MSCs)暴露于这些外切体，以评估外切体的摄取、细胞迁移和增殖。此外，还评估了纤维蛋白凝胶(即稀释的纤维蛋白密封剂)作为外切体的输送系统。我们的结果表明，外切体能吸引间充质干细胞，纤维蛋白凝胶增强了它们的作用。此外，外切体还能促进MSCs的增殖。因此，我们认为牙髓来源的外切体与纤维蛋白凝胶的结合可能是临床上向改进的无细胞再生牙髓移植的强有力的组合，从而代表了一种填充牙齿硬组织的新方法。
Regenerative endodontics has been described as a paradigm shift in dentistry, despite its current limitation to immature teeth and reparative rather than regenerative outcomes. Cell-free treatments are favored because of regulatory issues. However, the recruitment of host-derived stem cells to the desired site remains challenging. We investigated whether dental pulp-derived exosomes, which are extracellular vesicles that contain proteins, lipids, RNA, and DNA and thus mirror their parental cells, may be used for this purpose. The use of exosomes may present appreciable advantages over the direct use of transplanted stem cells due to a higher safety profile, easier isolation, preservation, and handling. Here we harvested exosomes from a cultured third-molar pulp cell and assessed them by transmission electron microscopy and Western blotting. Human mesenchymal stem cells (MSCs) were exposed to these exosomes to assess exosome uptake, cell migration, and proliferation. In addition, a fibrin gel (i.e., a diluted fibrin sealant), was assessed as a delivery system for the exosomes. Our results show that exosomes attracted MSCs, and the fibrin gel enhanced their effect. Moreover, exosomes improved the proliferation of MSCs. Therefore, we propose that pulp-derived exosomes in combination with a fibrin gel could be a powerful combination for clinical translation towards improved cell-free regenerative endodontics and thus represent a new way to fill dental hard tissues.