A novel three-dimensional model system for keloid study: Organotypic multicellular scar model
A novel three-dimensional model system for keloid study: Organotypic multicellular scar model
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DOI：
10.1111/j.1524-475x.2012.00869.x
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Yun, Chae-Ok
中科院分区：
文献类型：
--
作者：
Lee, Won Jai;Choi, Il-Kyu;Yun, Chae-Ok
我们建立了一个三维器官型多细胞球体瘢痕模型，以模拟人类瘢痕疙瘩组织的微环境。瘢痕疙瘩组织培养7天。在原代瘢痕疙瘩球体培养中，总细胞数和凋亡指数的变化分别用组织学和TUNEL法进行评价。用免疫组化法检测转化生长因子-β（TGF-β）、I型胶原、III型胶原、弹性蛋白、纤连蛋白、基质金属蛋白酶-2和基质金属蛋白酶-9的表达谱。此外，在用曲安奈德治疗原发性瘢痕疙瘩球状体后，研究了这些表达谱。离体培养的瘢痕疙瘩球状体的细胞活力和形态得以维持，并且细胞凋亡指数在培养中长达1周没有增加。离体培养的瘢痕疙瘩球状体保留了瘢痕疙瘩的主要特征，例如高水平的胶原蛋白I和TGF-β表达长达7天。在离体培养过程中，瘢痕疙瘩对TGF-β的生物活性也得以维持。此外，离体曲安奈德治疗培养的瘢痕疙瘩球状体显着降低胶原蛋白I，胶原蛋白III，弹性蛋白和纤连蛋白的表达水平，根据临床观察。三维器官型多细胞球形瘢痕疙瘩文化将使研究人员研究瘢痕疙瘩的发病机制和测试潜在的瘢痕疙瘩治疗药物。
We developed a three-dimensional organotypic multicellular spheroid scar model to mimic the microenvironment of human keloid tissues. Keloid tissues were cultured for 7 days. Changes in total cellularity and apoptotic index in the primary keloid spheroid cultures were evaluated histologically and with a TUNEL assay, respectively. The expression profiles of transforming growth factor-beta (TGF-beta), collagen I, collagen III, elastin, fibronectin, matrix metalloproteinase-2, and matrix metalloproteinase-9 were examined with immunohistochemistry. In addition, these expression profiles were investigated after treating primary keloid spheroids with triamcinolone acetonide. Cell viability and morphology of ex vivo cultured keloid spheroids were maintained, and the apoptotic index did not increase for up to 1 week in culture. Keloid spheroids cultivated ex vivo retained the major characteristics of keloids, such as high levels of collagen I and TGF-beta expression for up to 7 days. The biological activity of keloids responding to TGF-beta was also maintained during ex vivo culture. Moreover, ex vivo triamcinolone acetonide treatment of cultivated keloid spheroids significantly reduced collagen I, collagen III, elastin, and fibronectin expression levels, in accordance with clinical observations. The three-dimensional organotypic multicellular spheroid keloid culture will allow investigators to study keloid pathogenesis and test potential keloid therapeutic agents.