The influence of matrix properties on growth and morphogenesis of human pancreatic ductal epithelial cells in 3D.
The influence of matrix properties on growth and morphogenesis of human pancreatic ductal epithelial cells in 3D.
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基质特性对3D人类胰管上皮细胞生长和形态发生的影响。
DOI：
10.1016/j.biomaterials.2013.03.086
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发表时间：
2013-07
期刊：
影响因子：
14
通讯作者：
Lin, Chien-Chi
中科院分区：
文献类型：
--
作者：
Raza, Asad;Ki, Chang Seok;Lin, Chien-Chi
开发了一种高度可调的合成仿生水凝胶平台，以研究胰腺导管上皮细胞（PDEC）在无数指导性线索的影响下的生长和形态发生。PDEC系PANC-1用作模型系统以说明基质组成对细胞命运测定的重要性。PANC-1是一种永生化的导管上皮细胞系，广泛用于胰腺肿瘤细胞行为的研究。PANC-1细胞也越来越多地被探索为内分泌分化的潜在细胞来源。到目前为止，大多数与PANC-1以及其他PDEC系相关的研究都是在2D培养表面上进行的。在这里，我们评估了基质组合物对PANC-1细胞生长和3D形态发生的影响。具体地，PANC-1细胞被封装在通过逐步生长硫醇-烯光聚合制备的PEG基水凝胶中。发现硫醇-烯水凝胶为PANC-1细胞的包封和3D培养提供了细胞相容性环境。与2D培养表面上的单层形态相反，PANC-1细胞在培养的4天内在3D硫醇-烯水凝胶中形成簇。然而，培养10天后，这些簇的生长和结构受到凝胶基质性质的显著影响，包括基质对蛋白酶的敏感性、基质的刚度和ECM模拟基序。使用基质金属蛋白酶（MMP）敏感的连接体或在基质中固定纤连蛋白衍生的RGDS配体促进PANC-1细胞生长，并鼓励它们采用导管囊肿样结构。另一方面，封装的细胞在非MMP响应性凝胶中形成更小和更紧凑的聚集体。层粘连蛋白衍生的YIGSR肽的掺入没有增强细胞生长，并导致细胞形成紧凑的聚集体。固定化YIGSR还增强了上皮细胞标志物包括β-连环蛋白和E-钙粘蛋白的表达。这些研究已经建立了由硫醇-烯光点击反应形成的PEG-肽水凝胶，作为研究和操纵胰腺上皮细胞生长和3D形态发生的合适平台。
A highly tunable synthetic biomimetic hydrogel platform was developed to study the growth and morphogenesis of pancreatic ductal epithelial cells (PDEC) under the influence of a myriad of instructive cues. A PDEC line, PANC-1, was used as a model system to illustrate the importance of matrix compositions on cell fate determination. PANC-1 is an immortalized ductal epithelial cell line widely used in the study of pancreatic tumor cell behaviors. PANC-1 cells are also increasingly explored as a potential cell source for endocrine differentiation. Thus far, most studies related to PANC-1, among other PDEC lines, are performed on 2D culture surfaces. Here, we evaluated the effect of matrix compositions on PANC-1 cell growth and morphogenesis in 3D. Specifically, PANC-1 cells were encapsulated in PEG-based hydrogels prepared by step-growth thiol-ene photopolymerization. It was found that thiol-ene hydrogels provided a cytocompatible environment for encapsulation and 3D culture of PANC-1 cells. In contrast to a monolayer morphology on 2D culture surfaces, PANC-1 cells formed clusters in 3D thiol-ene hydrogels within 4 days of culture. After culturing for 10 days, however, the growth and structures of these clusters were significantly impacted by gel matrix properties, including sensitivity of the matrix to proteases, stiffness of the matrix, and ECM-mimetic motifs. The use of matrix metalloproteinase (MMP) sensitive linker or the immobilization of fibronectin-derived RGDS ligand in the matrix promoted PANC-1 cell growth and encouraged them to adopt ductal cyst-like structures. On the other hand, the encapsulated cells formed smaller and more compact aggregates in non-MMP responsive gels. The incorporation of laminin-derived YIGSR peptide did not enhance cell growth and caused the cells to form compact aggregates. Immobilized YIGSR also enhanced the expression of epithelial cell markers including β-catenin and E-cadherin. These studies have established PEG-peptide hydrogels formed by thiol-ene photo-click reaction as a suitable platform for studying and manipulating pancreatic epithelial cell growth and morphogenesis in 3D.
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影响因子：
8.8
作者：
Iwamoto, Y;Nomizu, M;Yamada, Y;Ito, Y;Tanaka, K;Sugioka, Y
通讯作者：
Sugioka, Y
DOI：
10.1016/j.bbrc.2008.12.080
发表时间：
2009-02-06
影响因子：
3.1
作者：
Binker, Marcelo G.;Binker-Cosen, Andres A.;Cosen-Binker, Laura I.
通讯作者：
Cosen-Binker, Laura I.
影响因子：
2.9
作者：
Arumugam T;Brandt W;Ramachandran V;Moore TT;Wang H;May FE;Westley BR;Hwang RF;Logsdon CD
通讯作者：
Logsdon CD
影响因子：
29.4
作者：
Fairbanks, Benjamin D;Schwartz, Michael P;Halevi, Alexandra E;Nuttelman, Charles R;Bowman, Christopher N;Anseth, Kristi S
通讯作者：
Anseth, Kristi S
影响因子：
3.7
作者：
Deharvengt S;Marmarelis M;Korc M
通讯作者：
Korc M