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Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration

机译:藻酸盐水凝胶共递送微囊化系统中封装的牙齿间充质干细胞用于软骨再生

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Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (p < 0.05). Taken together, these results suggest that RGD-modified alginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs.
机译:牙科来源的间充质干细胞(MSC)是软骨再生的有希望的候选者,具有高的软骨分化能力。与当前的治疗方式相比,该特性有助于使牙科MSC成为一种有利的治疗选择。 MSC传递载体是MSC介导的软骨再生疗法成功的主要决定因素。这项研究的目的是:(1)开发一种新型的基于TGF-β1的RGD偶联藻酸盐微球共包封系统,该微球包封牙周膜干细胞(PDLSC)或牙龈间充质干细胞(GMSC)。 (2)研究藻酸盐微球中牙科MSC的生存能力和软骨分化。结果表明TGF-β1从藻酸盐微球中持续释放。在体外软骨形成分化4周后,PDLSC和GMSC以及人骨髓间充质干细胞(hBMMSC)(作为阳性对照)通过qPCR揭示了软骨形成基因表达标记(Col II和Sox-9),并且基质呈阳性被甲苯胺蓝和番红O染色。在动物研究中,通过组织化学和免疫荧光染色证实了移植微球内部和周围的异位软骨组织再生。有趣的是,PDLSC比GMSC和hBMMSC显示出更多的软骨形成(p <0.05)。综上所述,这些结果表明,RGD修饰的藻酸盐微囊化牙科MSC成为软骨再生的有希望的候选者。我们的结果突出了微环境所发挥的至关重要的作用,以及呈现诱导信号对于MSC的生存能力和分化的价值。

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