Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
Biomaterials. 2014 Mar;35(9):2642-50. doi: 10.1016/j.biomaterials.2013.12.053. Epub 2014 Jan 4.
Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue's very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-β3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (P < 0.05). Altogether, these findings indicate that periodontal ligament and gingival tissues can be considered as suitable stem cell sources for tendon engineering. PDLSCs and GMSCs encapsulated in TGF-β3-loaded RGD-modified alginate microspheres are promising candidates for tendon regeneration.
肌腱损伤常伴有明显的功能障碍和残疾，这是由于肌腱组织自我修复能力非常有限，容易形成瘢痕。牙源性间充质干细胞（MSCs）与合适的支架材料相结合，为肌腱修复/再生提供了一种替代的治疗选择，可能优于其他当前的治疗方法。MSCs 的输送载体是成功实施 MSC 介导的再生治疗的主要决定因素。在本研究中，开发了一种基于负载 TGF-β3 的 RGD 偶联藻酸盐微球的共输送系统，用于包封牙周膜干细胞（PDLSCs）或牙龈间充质干细胞（GMSCs）。研究了包封的牙源性 MSCs 向肌腱组织分化的能力，进行了体外和体内研究。将包封的牙源性衍生 MSC 皮下移植到免疫缺陷小鼠中。研究结果显示，在体外分化 4 周后，通过 qPCR 测量，PDLSCs 和 GMSCs 以及阳性对照人骨髓间充质干细胞（hBMMSCs）的基因标记物相关的肌腱再生的 mRNA 表达水平均较高（Scx、DCn、Tnmd 和 Bgy）。在相应的动物模型中，通过组织学和免疫组织化学染色证实，在皮下移植的 MSC-藻酸盐构建体中观察到异位新腱再生，这些蛋白标记物是肌腱的特异性蛋白标记物。有趣的是，在我们的定量 PCR 和体内组织形态计量学分析中，PDLSCs 显示出比 GMSCs 或 hBMMSCs 更强的肌腱再生能力（P < 0.05）。总的来说，这些发现表明牙周膜和牙龈组织可以被认为是肌腱工程的合适干细胞来源。负载 TGF-β3 的 RGD 修饰藻酸盐微球包封的 PDLSCs 和 GMSCs 是肌腱再生的有前途的候选物。
