Crombleholme T M
Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104, USA.
Wound Repair Regen. 2000 Nov-Dec;8(6):460-72. doi: 10.1046/j.1524-475x.2000.00460.x.
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.
在考虑细胞因子和生长因子在正常伤口愈合反应中的重要作用之前，基因转移策略在伤口愈合中的应用并非这项技术的显而易见的用途。已经提出了几种基因转移策略，从体外逆转录病毒介导的基因转移与自体移植，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效率、转基因表达和生物学反应。腺病毒介导的基因转移在伤口愈合中是这种载体的一种相对较新的应用。腺病毒作为基因转移载体的优势在于其能够高效转导所有类型的非分裂细胞，而无需整合到宿主细胞基因组中。腺病毒作为载体的缺点是转基因表达持续时间相对较短以及它引发的炎症反应。在伤口愈合的情况下，短暂的高水平转基因表达可能是对伤口愈合产生有利影响所必需的全部条件。其次，由于伤口愈合从根本上说是一种炎症反应，只要转基因是具有显著愈合作用的生长因子，如血小板衍生生长因子 -B，腺病毒引发的炎症可能并无害处。本综述总结了腺病毒介导的基因转移在伤口愈合受损实验模型中的当前状态，这些模型为血小板衍生生长因子 -B 腺病毒介导的基因转移在慢性下肢静脉溃疡和慢性不愈合糖尿病足溃疡中的 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作用的有用工具。作为一种在纠正受损伤口愈合中有效递送生长因子的手段，腺病毒介导的基因转移在临床应用中可能具有重大前景。
