Keratin expression in cultured skin substitutes suggests that the hyperproliferative phenotype observed in vitro is normalized after grafting
Keratin expression in cultured skin substitutes suggests that the hyperproliferative phenotype observed in vitro is normalized after grafting
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DOI：
10.1016/j.burns.2005.08.017
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发表时间：
2006-03-01
期刊：
影响因子：
2.7
通讯作者：
Supp, DM
中科院分区：
文献类型：
--
作者：
Smiley, AK;Klingenberg, JM;Supp, DM
培养的皮肤替代物由成纤维细胞和角质形成细胞在生物聚合物基质中组成，是全面烧伤创面的辅助治疗。以往的研究表明，体外培养的皮肤替代物表现出类似于过度增殖的皮肤或损伤的正常皮肤的基因表达谱。在目前的研究中，我们试图确定在体内移植的培养皮肤愈合后这种过度增殖的表型是否保持。用免疫组织化学方法对天然人皮肤、体外培养的皮肤替代物和移植到裸鼠体内的多种角蛋白进行定位。角蛋白6、角蛋白16和角蛋白17在体外培养的皮肤替代物中高度表达，它们在角质形成细胞激活和过度增殖的表皮中高表达。这些蛋白质在天然人皮肤中很低或检测不到，而在移植后的培养皮肤中则减少了。相反，在体外培养的皮肤替代物中没有检测到角蛋白15，它在激活的角质形成细胞中下调，但在移植到小鼠身上后上调。这一结果证实了先前的观察结果，即体外培养的皮肤替代物存在过度增殖或激活的表型，类似于受伤的天然皮肤。在移植到裸鼠身上后，表达模式表明培养的皮肤替代品已经正常化，成为更接近于未受损伤的人类皮肤的表型。(C)2005年爱思唯尔有限公司和ISBI。版权所有。
Cultured skin substitutes, consisting of fibroblasts and keratinocytes in a biopolymer matrix, are an adjunctive treatment for full thickness burn wounds. Previous studies revealed that cultured skin substitutes in vitro exhibit a gene expression profile similar to hyperproliferative skin or wounded normal skin. In the present study, we sought to determine whether this hyperproliferative phenotype is maintained after healing of grafted cultured skin in vivo. Immunohistochemistry was used to localize multiple keratin proteins in native human skin, and in cultured skin substitutes in vitro and after grafting to athymic mice. Keratin 6. keratin 16, and keratin 17, which are known to be upregulated during keratinocyte activation and in hyperproliferative epidermis, were highly expressed in cultured skin substitutes in vitro. These proteins were low or undetectable in native human skin, and were reduced in Cultured skin after grafting. Conversely, keratin 15, which is downregulated in activated keratinocytes, was not detected in cultured skin substitutes in vitro but was upregulated after grafting to mice. The results confirm previous observations suggesting a hyperproliferative or activated phenotype in cultured skin substitutes in vitro, similar to wounded native skin. After grafting to athymic mice, the expression patterns suggest a normalization of cultured skin substitutes to a phenotype more closely resembling uninjured human skin. (c) 2005 Elsevier Ltd and ISBI. All rights reserved.