3D 丝素蛋白-明胶/透明质酸/硫酸乙酰肝素支架增强胆管癌细胞干性和 EMT 标志物的表达。
3D Silk Fibroin-Gelatin/Hyaluronic Acid/Heparan Sulfate Scaffold Enhances Expression of Stemness and EMT Markers in Cholangiocarcinoma.
机构信息
Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
出版信息
In Vivo. 2022 May-Jun;36(3):1155-1167. doi: 10.21873/invivo.12815.
BACKGROUND/AIM: Cholangiocarcinoma (CCA) is a stem cell-based cancer. The in vivo tumor microenvironment is not present in two-dimensional (2D) cultures, which is one of the limitations in cancer stem cell (CSC) research. Thus, we aimed to establish three-dimensional (3D) culture mimicking extracellular matrix (ECM) that could serve as a niche for CSC enrichment in CCA.
MATERIALS AND METHODS
Silk fibroin-gelatin/hyaluronic acid/heparan sulfate (SF-GHHs) scaffolds were fabricated by lyophilization in various ratios and compared to silk fibroin (SF) scaffold. The physical and biological characteristics of the scaffolds were investigated.
RESULTS
The SF-GHHs 1:2 scaffold with pore size of 350±102 μm harbored optimal porosity, good water uptake, and stable beta-sheet that supported the increase in KKU-213A cell proliferation and aggregation. The CSC and the epithelial-mesenchymal transition (EMT) markers were significantly upregulated in this scaffold compared to 2D. Moreover, drug sensitivity against cisplatin and gemcitabine in 3D culture was significantly higher than that in 2D culture.
CONCLUSION
The SF-GHHs 1:2 scaffold could simulate ECM that may serve as a CSC niche of CCA, and reinforce stemness and EMT properties, suggesting its suitability for 3D CCA model, which supports CSC and new targeting drug research in CCA.
背景/目的：胆管癌（CCA）是一种基于干细胞的癌症。二维（2D）培养中不存在体内肿瘤微环境，这是癌症干细胞（CSC）研究的局限性之一。因此，我们旨在建立三维（3D）培养物，模拟细胞外基质（ECM），以作为 CCA 中 CSC 富集的龛位。
材料与方法
通过冷冻干燥法以不同比例制备丝素蛋白-明胶/透明质酸/硫酸乙酰肝素（SF-GHHs）支架，并与丝素蛋白（SF）支架进行比较。研究了支架的物理和生物学特性。
结果
SF-GHHs 1:2 支架的孔径为 350±102 μm，具有最佳的孔隙率、良好的吸水性和稳定的β-折叠，支持 KKU-213A 细胞增殖和聚集的增加。与 2D 相比，该支架中 CSC 和上皮-间充质转化（EMT）标志物显著上调。此外，3D 培养中的顺铂和吉西他滨药物敏感性明显高于 2D 培养。
结论
SF-GHHs 1:2 支架可以模拟 ECM，可能作为 CCA 的 CSC 龛位，增强干细胞特性和 EMT 特性，表明其适合用于 3D CCA 模型，支持 CCA 中的 CSC 和新型靶向药物研究。
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