FGF-7 expression enhances the performance of bioengineered skin

FGF-7 expression enhances the performance of bioengineered skin
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DOI:
10.1016/j.ymthe.2004.04.013
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发表时间:
2004-07-01
期刊:
影响因子:
12.4
通讯作者:
Morgan, JR
Morgan, JR
中科院分区:
医学1区
文献类型:
--
作者:
Erdag, G;Medalie, DA;Morgan, JR

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为了改善生物工程皮肤的性能,我们使用编码成纤维细胞生长因子-7的重组逆转录病毒对二倍体人角质形成细胞进行基因修饰。将对照组或表达成纤维细胞生长因子-7的角质形成细胞接种到脱细胞人真皮上,形成生物工程皮肤。基因修饰的皮肤分泌大量的成纤维细胞生长因子-7,并形成更厚和过度增殖的表皮,每平方厘米的细胞数量约为4倍。内源性营养因子血管内皮生长因子的分泌增加了近5倍。表达成纤维细胞生长因子-7的角质形成细胞的迁移被刺激,表达成成纤维细胞生长因子-7的生物工程皮肤的自愈也被刺激。当在细菌感染模型中进行测试时,表达成纤维细胞生长因子-7的皮肤对革兰氏阴性和革兰氏阳性细菌的抗菌性能都提高了500倍。移植到裸鼠的全层创面后,表达成纤维细胞生长因子-7的皮肤血运重建更快。这些结果表明,基因改造可以用来提高性能,而且表达成纤维细胞生长因子-7可以增强一些对生物工程皮肤的伤口愈合特性很重要的特性。
To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically. Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin. Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter. Secretion of an endogenous trophic factor, VEGF, was increased similar to5-fold. Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7. When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria. After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly. These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin.