Matrix-enabled gene transfer for cutaneous wound repair
Matrix-enabled gene transfer for cutaneous wound repair
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DOI：
10.1046/j.1524-475x.2000.00473.x
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发表时间：
2000-11-01
影响因子：
2.9
通讯作者：
Phillips, ML
中科院分区：
文献类型：
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作者：
Chandler, LA;Gu, DL;Phillips, ML
几种生长因子蛋白质已被评估为用于治疗慢性皮肤伤口的治疗剂。不幸的是，大多数未能产生伤口愈合的显著改善，部分原因是无效的递送和在伤口缺损中的不良保留。有人提出，基因治疗可以通过持续的转录和翻译来克服蛋白质治疗的局限性，从而延长治疗蛋白的可用性。推断确保DNA载体以及治疗性蛋白质保留在伤口缺损内将是进一步有益的。我们已经评价了用于皮肤创伤修复的基质激活的基因转移（基因激活的基质）。已在3种体内模型中评价了由牛I型胶原蛋白与腺病毒或质粒基因载体混合组成的制剂。所采用的治疗性转基因编码人血小板衍生生长因子-A或-B，这些蛋白质是正常伤口修复的每个阶段的关键。与单独使用胶原蛋白或含有报告基因载体的胶原蛋白处理的对照相比，已显示肉芽组织形成、血管形成和上皮再生增加。组织修复反应的进一步增强已经通过将基质使能的基因转移与分子靶向结合来实现，其中DIVA载体与生长因子配体（碱性成纤维细胞生长因子）缀合。这些有希望的结果支持基因活化基质用于治疗慢性皮肤伤口的临床评价。
Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect. we have evaluated matrix-enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet derived growth factor-A or -B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix-enabled gene transfer with molecular targeting, in which the DIVA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds.