Epidermal growth factor mediated healing in stem cell-derived vocal fold mucosa.

Epidermal growth factor mediated healing in stem cell-derived vocal fold mucosa.
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DOI:
10.1016/j.jss.2015.02.066
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发表时间:
2015-07
影响因子:
2.2
通讯作者:
Leydon, Ciara
Leydon, Ciara
中科院分区:
医学3区
文献类型:
--
作者:
Palencia, Liliana;Das, Amritava;Palecek, Sean P.;Thibeault, Susan L.;Leydon, Ciara

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声带伤口愈合的目的是重建功能组织,包括结构和功能完整的上皮。声带上皮再生的机制尚不清楚,尽管人们怀疑其愈合涉及几种生长因子之间的相互作用。我们使用一个三维人胚胎干细胞衍生的声带粘膜模型来研究一种生长因子,外源性表皮生长因子(EGF)对伤口愈合的影响。在体外模型中建立抓伤伤口。研究人员分析了外源性表皮生长因子受体(EGFR)和EGFR抑制剂吉非替尼对伤口愈合、表皮生长因子受体(EGFR)激活和损伤后细胞增殖的影响。与没有外源性EGF(7.1µm/小时±2.84)相比,外源性EGF(13.3µm/小时,±2.63)显著加速了损伤后的伤口修复,但同时添加吉非替尼(5.2µm/小时,±2.23)会抑制伤口修复,这表明EGF以egfr依赖的方式介导伤口愈合。免疫组织化学显示,EGFR激活仅在外源性EGF存在时发生。虽然没有统计学意义,但在使用EGF治疗后,观察到抓伤伤口附近上皮中Ki67染色密度增加,这表明外源性EGF有增加上皮细胞增殖的趋势。在三维干细胞衍生的声带粘膜模型中,外源性EGF以egfr依赖的方式增加伤口愈合的速度。这种伤口愈合模型可用于深入了解损伤后声带上皮修复的调节机制。
The goal of vocal fold wound healing is the reconstitution of functional tissue, including a structurally and functionally intact epithelium. Mechanisms underlying reepithelialization in vocal folds are not known, although it is suspected that healing involves the interplay between several growth factors. We used a three-dimensional human embryonic stem cell-derived model of vocal fold mucosa to examine the effects of one growth factor, exogenous epidermal growth factor (EGF), on wound healing. A scratch wound was created in the in vitro model. Rate of wound healing, epidermal growth factor receptor (EGFR) activation, and cell proliferation post-injury were analyzed with and without application of both exogenous EGF and an EGFR inhibitor, Gefitinib. Wound repair after injury was significantly hastened by application of exogenous EGF (13.3 µm/hour, ±2.63) compared to absence of exogenous EGF (7.1 µm/hour ±2.84), but inhibited with concurrent addition of Gefitinib (5.2 µm/hour, ±2.23), indicating that EGF mediates wound healing in an EGFR-dependent manner. Immunohistochemistry revealed that EGFR activation occurred only in the presence of exogenous EGF. While not statistically significant, increased density of Ki67 staining in epithelium adjacent to the scratch wound was observed following treatment with EGF, suggesting a tendency for exogenous EGF to increase epithelial cell proliferation. Exogenous EGF increases the rate of wound healing in an EGFR-dependent manner in a three-dimensional stem cell-derived model of vocal fold mucosa. This model of wound healing can be used to gain insight into the mechanisms that regulate vocal fold epithelial repair following injury.
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