Adenoviral-mediated gene transfer in wound healing
Adenoviral-mediated gene transfer in wound healing
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DOI：
10.1046/j.1524-475x.2000.00460.x
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发表时间：
2000-11-01
影响因子：
2.9
通讯作者：
Crombleholme, TM
中科院分区：
文献类型：
--
作者：
Crombleholme, TM
基因转移策略在伤口愈合中的应用并不是这种技术的明显用途，直到人们考虑到细胞因子和生长因子在正常伤口愈合反应中的重要作用。已经提出了几种基因转移策略，从体外逆转录病毒介导的自体移植基因转移，到体内基于质粒的基因转移，如逆转录病毒基因转移。这些方法的局限性在于基因转移、转基因表达和生物反应的效率。腺病毒介导的基因转移在伤口愈合中是这种载体的一个相对较新的应用。腺病毒作为基因转移载体的优势在于它能够以非常高的效率转染所有类型的非分裂细胞而不整合到宿主细胞的基因组中。腺病毒作为载体的缺点是转基因表达的持续时间相对较短，并且引起炎症反应。在伤口愈合的背景下，短暂的高水平转基因持续时间可能是有利地影响伤口愈合所必需的。其次，由于伤口愈合基本上是炎症反应，因此只要转基因是具有显著促炎作用的生长因子，如血小板衍生生长因子-B，由腺病毒引发的炎症可能不是有害的。本文综述了腺病毒介导的基因转移在伤口愈合受损的实验模型中的现状，这些模型为腺病毒介导的血小板源性生长因子-B基因转移治疗慢性下肢静脉溃疡和慢性不愈合糖尿病足溃疡的I期临床试验奠定了基础。腺病毒介导的基因转移是研究特定细胞因子和生长因子在正常和受损伤口愈合中的作用的有用工具。腺病毒介导的基因转移作为一种有效的生长因子递送手段在纠正受损的伤口愈合中的临床应用可能具有重要的前景。
The application of gene transfer strategies to wound healing is not an obvious use of this technology until one considers the important role of cytokines and growth factors in the normal wound healing response. Several gene transfer strategies have been proposed, from in vitro retroviral-mediated gene transfer with autologous transplantation, to in vivo plasmid based gene transfer as retroviral gene transfer. The limitations of these approaches have been efficiency of gene transfer, transgene expression and biologic response. Adenoviral-mediated gene transfer in wound healing is a relatively new application of this vector. The advantage of the adenovirus as a gene transfer vector lies in its ability to transduce nondividing cells of all types at very high efficiency without integration into the host cell's genome. The disadvantage of adenovirus as a vector is the relatively short duration of transgene expression and the inflammatory response it elicits. In the setting of wound healing brief duration of high levels of transgene may be all that is necessary to favorably influence wound healing. Secondly, as wound healing is fundamentally an inflammatory response, the inflammation elicited by the adenovirus may not be detrimental as long as the transgene is a growth factor with significant vulnerary effects such as platelet-derived growth factor-B. This review summarizes the current state of adenoviral-mediated gene transfer in experimental models of impaired wound healing which have laid the groundwork for proposed phase I clinical trials of adenoviral-mediated gene transfer of platelet-derived growth factor-B in chronic venous leg ulcers and chronic nonhealing diabetic foot ulcers. Adenoviral-mediated gene transfer is a useful tool in the study of the role of specific cytokines and growth factors in normal and impaired wound healing. Adenoviral-mediated gene transfer may hold significant promise for clinical application as a means of efficient growth factor delivery in correcting impaired wound healing.