Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration
Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration
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DOI：
10.1016/j.jcyt.2014.11.009
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发表时间：
2015-04-01
期刊：
影响因子：
4.5
通讯作者：
Ueda, Minoru
中科院分区：
文献类型：
--
作者：
Kawai, Takamasa;Katagiri, Wataru;Ueda, Minoru
背景目标。利用间充质基质细胞(MSCs)再生牙周组织被认为是一种未来的细胞治疗方法。然而，低存活率和移植的MSCs的潜在致瘤性可能会削弱基于细胞的治疗效果。使用来自MSCs的条件培养液(MSC-CM)可能是克服这些限制的可行方法。本研究的目的是证实MSC-CM在牙周再生中的作用。方法：研究方法。在培养过程中收集MSC-CM。采用酶联免疫分析法检测MSC-CM中生长因子的浓度。用MSC-CM培养大鼠骨髓间充质干细胞(RMSCs)和人脐静脉内皮细胞，观察创面愈合和血管生成情况。采用实时定量逆转录聚合酶链式反应技术，定量检测MSC-CM培养的rMSCs成骨和血管生成相关基因的表达。体内制备大鼠牙周组织缺损模型，植入含有MSC-CM的胶原海绵。结果。MSC-CM包括胰岛素样生长因子-1、血管内皮生长因子、转化生长因子-β1和肝细胞生长因子。在体外，MSC-CM的创面愈合和血管生成显著增加。在MSC-CM培养的rMSCs中，成骨和血管生成相关基因的表达水平显著上调。在体内，MSC-CM组在植入后2周免疫组织化学分析显示，CD31、CD105或Flk-1阳性细胞频繁出现。种植后4周，MSC-CM组可见牙周组织再生。结论。MSC-CM的使用可能是牙周组织再生的一种替代疗法，因为MSC-CM中包含的几种细胞因子将参与许多复杂的牙周组织再生过程。
Background aims. Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration. Methods. MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted. Results. MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-beta 1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD 105- or FLK-1 positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups. Conclusions. The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration.