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取向地形介导的细胞伸长可逆转体外培养瘢痕疙瘩成纤维细胞的病理性表型。

Aligned topography mediated cell elongation reverses pathological phenotype of in vitro cultured keloid fibroblasts.

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Tissue Engineering Research, National Tissue Engineering Center of China, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

出版信息

J Biomed Mater Res A. 2019 Jul;107(7):1366-1378. doi: 10.1002/jbm.a.36650. Epub 2019 Feb 28.

Abstract

Topography modified cell behavior remains less explored in diseased cells. This study investigated the reversing effect on the pathological phenotype of keloid fibroblasts via culturing cells on a parallel microgrooved surface. The results showed that this particular topography with 3 μm groove depth and 10 μm width could significantly elongate and align the cultured cells with reduced cell (nucleus) area and increased cell (nucleus) body aspect ratio and cell (nucleus) body major axis (p < 0.05). Importantly, the elongated cells gradually lost their fibrotic phenotype with inhibited cell proliferation and cell cycle arrest in S-phase (p < 0.05), reduced expression of fibrotic markers such as collagen, fibronectin, connective tissue growth factor, α-smooth muscle actin, transforming growth factor-β1 (p < 0.05), and increased matrix metalloproteinases/tissue inhibitor-1 ratio (p < 0.05) along with attenuated Smad and Erk phosphorylation level. All these indicate that this parallel topography is powerful enough to modify keloid cell phenotype, a benign skin tumor with excessive cell proliferation and matrix production. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

摘要

在病变细胞中,地形修饰后的细胞行为变化研究还较少。本研究通过在平行微槽表面培养细胞,调查其对瘢痕成纤维细胞病理表型的逆转作用。结果表明,这种具有 3μm 槽深和 10μm 宽的特殊形貌能够显著拉长并排列培养细胞,降低细胞核面积,增加细胞核体纵横比和细胞核体长轴(p<0.05)。重要的是,逐渐拉长的细胞增殖能力减弱,S 期细胞周期停滞(p<0.05),纤维化标志物如胶原蛋白、纤维连接蛋白、结缔组织生长因子、α-平滑肌肌动蛋白、转化生长因子-β1(p<0.05)的表达减少,基质金属蛋白酶/组织抑制剂-1 比值增加(p<0.05),同时 Smad 和 Erk 磷酸化水平降低。所有这些都表明这种平行的形貌足以修饰瘢痕疙瘩细胞的表型,瘢痕疙瘩是一种良性皮肤肿瘤,具有过度的细胞增殖和基质产生。©2019 Wiley Periodicals, Inc. J 生物材料研究 A 部分,2019 年。

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