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首页> 外文期刊>Biomaterials >The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing.
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The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing.

机译:纤维蛋白E在调节内皮祖细胞黏附,分化和血管生成生长因子产生以及促进伤口愈合方面的作用。

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摘要

Severe skin loss constitutes a major unsolved clinical problem worldwide. For this reason, in the last decades there has been a major push towards the development of novel therapeutic approaches to enhance skin wound healing. Neo-vessel formation through angiogenesis is a critical step during the wound healing process. Besides the contribution of pre-existing endothelial cells (EC), endothelial progenitor cells (EPCs) have also been implicated in wound healing acting either by differentiating into EC that incorporate the neo-vessels, or via the production of paracrine factors that improve angiogenesis. Here we tested the importance of different extracellular matrices (ECM) in regulating the angiogenic and wound healing potential of cord blood-derived EPC (CB-EPC). We compared the properties of several ECM and particularly of fibrin fragment E (FbnE) in regulating EPC adhesion, proliferation, differentiation and healing-promotion in vitro and in vivo. Our results show that CB-EPCs have increased adhesion and endothelial differentiation when plated on FbnE compared to collagens, fibronectin or fibrin. Using integrin neutralizing antibodies, we show that CB-EPC adhesion to FbnE is mediated by integrin alpha5beta1. Gene expression analysis of CB-EPCs plated on different substrates revealed that CB-EPC grown on FbnE shows increased expression of paracrine factors such as VEGF-A, TGF-beta1, SDF-1, IL-8 and MIP-1alpha. Accordingly, conditioned media from CB-EPC grown on FbnE induced EC tube formation and monocyte migration in vitro. To test the wound healing effects of FbnE in vivo we used an FbnE enriched scaffold in a cutaneous wound healing mouse model. In accordance with our in vitro data, co-administration of the FbnE enriched scaffold with CB-EPC significantly accelerated wound closure and wound vascularization, compared FbnE enriched scaffold alone or to using collagen-based scaffolds. Our results show that FbnE modulates several CB-EPC properties in vivo and in vitro, and as such promotes wound healing. We suggest the use of FbnE-based scaffolds represents a promising approach to resolve wound healing complications arising from different pathologies.
机译:严重的皮肤损失是世界范围内尚未解决的主要临床问题。由于这个原因,在过去的几十年中,已经大力推动了开发新的治疗方法以增强皮肤伤口的愈合。通过血管生成的新血管形成是伤口愈合过程中的关键步骤。除了已有的内皮细胞(EC)的贡献外,内皮祖细胞(EPC)还通过参与新血管的分化为EC或通过产生改善血管生成的旁分泌因子参与伤口愈合。在这里,我们测试了不同细胞外基质(ECM)在调节脐血来源EPC(CB-EPC)的血管生成和伤口愈合潜力中的重要性。我们比较了几种ECM,特别是纤维蛋白片段E(FbnE)在体外和体内调节EPC粘附,增殖,分化和愈合促进方面的特性。我们的结果表明,与胶原蛋白,纤连蛋白或血纤蛋白相比,将CB-EPCs涂在FbnE上具有增强的粘附力和内皮分化。使用整合素中和抗体,我们表明CB EPC粘附到FbnE是由整合素alpha5beta1介导的。镀在不同底物上的CB-EPC的基因表达分析表明,生长在FbnE上的CB-EPC显示旁分泌因子(例如VEGF-A,TGF-β1,SDF-1,IL-8和MIP-1alpha)的表达增加。因此,在FbnE上生长的CB-EPC的条件培养基在体外诱导EC管形成和单核细胞迁移。为了在体内测试FbnE的伤口愈合效果,我们在皮肤伤口愈合小鼠模型中使用了富含FbnE的支架。根据我们的体外数据,与单独使用FbnE富集的支架或使用基于胶原的支架相比,富集FbnE的支架与CB-EPC共同给药可显着加速伤口闭合和伤口血管生成。我们的结果表明,FbnE在体内和体外可调节多种CB-EPC特性,因此可促进伤口愈合。我们建议使用基于FbnE的支架代表一种有前途的方法来解决由不同病理引起的伤口愈合并发症。

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