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热敏感水凝胶递送过表达血小板衍生生长因子-BB 的人牙周干细胞增强牙槽骨缺损修复。

Thermosensitive Hydrogel Delivery of Human Periodontal Stem Cells Overexpressing Platelet-Derived Growth Factor-BB Enhances Alveolar Bone Defect Repair.

机构信息

Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, People's Republic of China.

Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People's Republic of China.

出版信息

Stem Cells Dev. 2019 Dec 15;28(24):1620-1631. doi: 10.1089/scd.2019.0184. Epub 2019 Dec 2.

DOI:10.1089/scd.2019.0184
PMID:31663419
Abstract

Alveolar bone defects can arise as a consequence of trauma, infection, periodontal disease, or congenital alveolar fenestration. Many approaches have been employed in an effort to treat or overcome such defects, but the ability to effectively achieve alveolar regeneration remains elusive. Platelet-derived growth factor-BB (PDGF-BB) has been shown to serve as a key factor capable of orchestrating cell proliferation, angiogenesis, and chemoattraction in the context of osteogenic processes. Exactly how PDGF-BB affects human periodontal ligament stem cells (hPDLSCs), however, requires further exploration. In this report, we utilized a lentiviral construct to achieve PDGF-BB overexpression in hPDLSCs, allowing us to establish that this gene was able to enhance the proliferation of these cells and to mediate osteogenic gene upregulation therein. In addition, we established a rat model of alveolar defects that were implanted using different complexes, and then monitored through histological and micro-CT analyses 4 and 8 weeks postsurgery to assess bone repair outcomes. These analyses revealed that a thermosensitive hydrogel was an effective 3D cell culture scaffold, while PDLSCs overexpressing PDGF-BB enhanced bone growth in the context of alveolar bone defects. Together, these results thus indicate that PDGF-BB represents a potent means of promoting stem cell-based alveolar bone tissue regeneration.

摘要

牙槽骨缺损可由创伤、感染、牙周病或先天性牙槽窗引起。为了治疗或克服这些缺陷,已经采用了许多方法,但有效地实现牙槽骨再生的能力仍然难以捉摸。血小板衍生生长因子-BB(PDGF-BB)已被证明是一种关键因子,能够在成骨过程中协调细胞增殖、血管生成和趋化作用。然而,PDGF-BB 如何影响人牙周膜干细胞(hPDLSCs)还需要进一步探索。在本报告中,我们利用慢病毒构建体实现了 hPDLSCs 中的 PDGF-BB 过表达,从而证明该基因能够增强这些细胞的增殖,并介导其中成骨基因的上调。此外,我们建立了牙槽骨缺损的大鼠模型,使用不同的复合物进行植入,并在手术后 4 和 8 周通过组织学和 micro-CT 分析进行监测,以评估骨修复结果。这些分析表明,温敏水凝胶是一种有效的 3D 细胞培养支架,而过表达 PDGF-BB 的牙周膜干细胞增强了牙槽骨缺损中的骨生长。总之,这些结果表明 PDGF-BB 是促进基于干细胞的牙槽骨组织再生的有效手段。

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