首页> 外文期刊>Journal of plastic, reconstructive & aesthetic surgery: JPRAS >Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-beta receptor II.
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Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-beta receptor II.

机译:通过显性阴性TGF-β受体II的逆转录病毒递送减少肥厚性瘢痕。

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摘要

Effective blockade of the pluripotent cytokine transforming growth factor (TGF)-beta as a means of cutaneous scar reduction is a strategy with great potential. This desired effect may be achieved through the overexpression of mutant TGF-beta receptors within the wound milieu. Our goal was to examine the effects of dominant negative mutant TGF-beta receptor II (TGFbetaRIIdn) protein expression in a well-established rabbit ear model of hypertrophic scarring. Serial injections of a retroviral construct encoding a truncated TGFbetaRII and the marker green fusion protein (pMSCV-rIIdn-GFP) were performed in 7mm punch wounds at day 10 and day 12 (two-day injection group) or days 8, 10, 12 (three-day injection group) post-wounding. Delivery of an empty vector (pMSCV-GFP) at the same time points served as a negative control. Histomorphometric analysis of wounds harvested at day 28 revealed a modest, though statistically significant reduction (20%, p=0.027) in the scar elevation index (SEI) in two-day treated and a more modest reduction in SEI (12%) in the three-day treated arm compared to null-treated controls. Confocal microscopy confirmed stable, yet variable transfection of the construct in both peri-wound tissue as well as rabbit dermal fibroblasts transfected in vitro. Optimisation of this novel application in retroviral gene therapy could lead to effective anti-scarring strategies.
机译:有效阻断多能细胞因子转化生长因子(TGF)-β作为减少皮肤瘢痕的手段是一种具有巨大潜力的策略。可以通过在伤口环境中过量表达突变型TGF-β受体来达到所需的效果。我们的目标是在建立良好的肥厚性瘢痕兔耳模型中研究显性负突变TGF-β受体II(TGFbetaRIIdn)蛋白表达的影响。在第10天和第12天(两天注射组)或第8、10、12天(7天),在7mm穿孔创口中连续注射编码截短的TGFbetaRII和标志物绿色融合蛋白(pMSCV-rIIdn-GFP)的逆转录病毒构建体。三天注射组)伤后。空载体(pMSCV-GFP)在相同时间点的递送用作阴性对照。在第28天收获的伤口的组织形态计量学分析显示,尽管在两天的治疗中疤痕升高指数(SEI)在统计学上有显着降低(20%,p = 0.027),而在治疗后的第二天SEI降低幅度较小(12%)。与未治疗对照组相比,三天治疗组。共聚焦显微镜证实了该构建体在伤口周围组织以及体外转染的兔真皮成纤维细胞中稳定但可变的转染。逆转录病毒基因治疗中这种新应用程序的优化可能会导致有效的抗瘢痕形成策略。

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