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一种新型的人源化瘢痕疙瘩小鼠模型。

A novel model of humanised keloid scarring in mice.

机构信息

Institute of Basic Medical Sciences, General Hospital of PLA, Beijing, P.R. China.

Key Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to General Hospital of PLA, Beijing, P. R. China.

出版信息

Int Wound J. 2018 Feb;15(1):90-94. doi: 10.1111/iwj.12838. Epub 2017 Oct 27.

Abstract

Treatments for keloid scarring are a major challenge to scientists and physicians for their unknown aetiology. Although several models, including monolayer cell culture to tissue-engineered models, were developed, further research on keloid has more or less been hindered by the lack of appropriate animal models. Because these aberrant scars are specific to humans, we obtained human normal and keloid skin tissues and isolated dermal fibroblasts from them. Cell morphology, growth and immunohistochemical staining of myofibroblastmarker α-SMA were examined, and the cell medium of 2-hour culture and 24-hour culture was implanted on the back of nude mice. The cell medium of 2-hour culture and 24-hour culture was also analysed by a protein array for the detection of distinction in inflammatory factors. We showed that keloid fibroblasts had similar morphology and growth compared to normal skin fibroblasts, but the α-SMA expression was obviously up-regulated. After 6 weeks, mice of the 2-hour keloid-derived culture medium group exhibited keloid-like hypertrophic nodules macroscopically, while mice of 24-hour keloid-derived culture medium group were similar to normal skin. Histological findings confirmed that the reconstituted skin tissues had the typical features of human keloids. The protein array data revealed that RANTES were involved in humanised fibrotic occurrence in mice, also suggesting they were important modulators of this inflammatory event. This novel model might help to understand the key events that result in the formation of these abnormal scars and provide new therapeutic options.

摘要

瘢痕疙瘩的治疗是科学家和医生面临的主要挑战,因为其病因不明。尽管已经开发出几种模型,包括单层细胞培养到组织工程模型,但由于缺乏合适的动物模型,对瘢痕疙瘩的进一步研究或多或少受到了阻碍。由于这些异常疤痕是人类特有的,我们从人类正常和瘢痕疙瘩皮肤组织中分离出真皮成纤维细胞。检查了细胞形态、成纤维细胞生长和肌成纤维细胞标志物α-SMA 的免疫组织化学染色,并将 2 小时培养和 24 小时培养的细胞培养基植入裸鼠背部。还通过蛋白质阵列分析了 2 小时培养和 24 小时培养的细胞培养基,以检测炎症因子的差异。我们表明,瘢痕疙瘩成纤维细胞的形态和生长与正常皮肤成纤维细胞相似,但 α-SMA 表达明显上调。6 周后,2 小时瘢痕来源培养物组的小鼠表现出宏观上类似瘢痕疙瘩的肥大性结节,而 24 小时瘢痕来源培养物组的小鼠与正常皮肤相似。组织学发现证实,重建的皮肤组织具有人类瘢痕疙瘩的典型特征。蛋白质阵列数据显示 RANTES 参与了人类纤维化在小鼠中的发生,这也表明它们是这种炎症事件的重要调节剂。这种新模型可能有助于了解导致这些异常疤痕形成的关键事件,并提供新的治疗选择。

相似文献

1
A novel model of humanised keloid scarring in mice.一种新型的人源化瘢痕疙瘩小鼠模型。
Int Wound J. 2018 Feb;15(1):90-94. doi: 10.1111/iwj.12838. Epub 2017 Oct 27.
3
Reconstitution of Human Keloids in Mouse Skin.人瘢痕疙瘩在小鼠皮肤中的重建。
Plast Reconstr Surg Glob Open. 2017 Apr 25;5(4):e1304. doi: 10.1097/GOX.0000000000001304. eCollection 2017 Apr.

本文引用的文献

7
Keloid pathogenesis and treatment.瘢痕疙瘩的发病机制与治疗
Plast Reconstr Surg. 2006 Jan;117(1):286-300. doi: 10.1097/01.prs.0000195073.73580.46.

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