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首页> 外文期刊>Biomaterials Science >Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagenbased biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model
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Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagenbased biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model

机译：白细胞介素10和装饰蛋白基因的局部颞介递送使用胶原蛋白的双相支架和装饰素基因调节兔耳肥大瘢痕模型中TGF-β1/β2的表达

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摘要

Hypertrophic scarring (HS) is an intractable complication associated with cutaneous wound healing. Although transforming growth factor β1 (TGF-β1) has long been documented as a central regulatory cytokine in fibrogenesis and fibroplasia, there is currently no cure. Gene therapy is emerging as a powerful tool to attenuate the overexpression of TGF-β1 and its signaling activities. An effective approach may require transferring multiple genes to regulate different aspects of TGF-β1 signaling activities in a Spatiotemporal manner. Herein we report the additive anti-fibrotic effects of two plasmid DNAs encoding interleukin 10 (IL-10) and decorin (DCN) co-delivered via a biphasic 3D collagen scaffold reservoir platform. Combined gene therapy significantly attenuated inflammation and extracellular matrix components' accumulation in a rabbit ear ulcer model; and suppressed the expressions of genes associated with fibrogenesis, including collagen type I, as well as TGF-β1 and TGF-β2, while enhancing the genes commonly associated with regenerative healing including collagen type III. These findings may serve to provide a non-viral gene therapy platform that is safe, optimized, and effective to deliver multiple genes onto the diseased tissue in a wider range of tissue fibrosis-related maladies.
机译：肥厚性瘢痕（HS）是一种与皮肤伤口愈合相关的难治性并发症。虽然转化的生长因子β1（TGF-β1）长期被记录为纤维发生和纤维形成的中枢调节细胞因子，但目前没有固化。基因治疗是作为一种强大的工具，以衰减TGF-β1的过表达及其信号传导。有效的方法可能需要转移多个基因以以时尚的方式调节TGF-β1信号传导活动的不同方面。在此，我们报告了通过双相3D胶原屑储存器平台共同递送的两种质粒DNA的添加剂抗纤维化作用。结合基因治疗显着减弱了兔耳溃疡模型中的炎症和细胞外基质组分的积累;并且抑制了与纤维发生相关的基因的表达，包括胶原I型，以及TGF-β1和TGF-β2，同时增强与再生愈合有关的基因，包括胶原III型。这些发现可以提供一种非病毒基因治疗平台，该平台是安全，优化的，并且有效地将多个基因递送到患者纤维化相关的疾病中的患病组织上。

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  • 来源
    《Biomaterials Science》 |2021年第8期|共14页
  • 作者

    Ciarstan McArdle; Sunny Akogwu Abbah; Sirsendu Bhowmick; Estelle Collin; Abhay Pandit;

  • 作者单位

    CURAM SFI Research Centre for Medical Devices National University of Ireland Galway Ireland;

    CURAM SFI Research Centre for Medical Devices National University of Ireland Galway Ireland;

    CURAM SFI Research Centre for Medical Devices National University of Ireland Galway Ireland;

    CURAM SFI Research Centre for Medical Devices National University of Ireland Galway Ireland;

    CURAM SFI Research Centre for Medical Devices National University of Ireland Galway Ireland;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 计量学;
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