Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels.
Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels.
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DOI：
10.1016/j.biomaterials.2009.08.031
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发表时间：
2009-12
期刊：
影响因子：
14
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Benton, Julie A.;Fairbanks, Benjamin D.;Anseth, Kristi S.
瓣膜间质细胞（VIC）维持功能性心脏瓣膜结构，并显示短暂的成纤维细胞和肌成纤维细胞特性。大多数细胞表征研究都是在塑料培养皿上进行的;虽然这些系统很有见地，但也很有限。因此，基质金属蛋白酶（MMP）可降解的聚（乙二醇）（PEG）水凝胶系统提出了在此通信作为一个有用的工具，用于表征维克功能的3D。当被封装时，VIC获得扩散形态，并且增殖和迁移，如通过实时细胞显微镜所示。此外，将纤连蛋白衍生的悬垂RGD掺入系统中以促进整联蛋白结合。随着RGD浓度从0增加到2000 μM，维克过程延伸和整合素αvβ3结合在两天内增加。到第10天，整合素结合在条件之间均衡。维克形态和速度的过程扩展也增加了通过降低水凝胶基质密度呈现给细胞。还在水凝胶网络内检查了响应于外源性递送的转化生长因子-β 1（TGF-β1）的维克分化。TGF-β1在培养第2天增加α平滑肌肌动蛋白（αSMA）和胶原蛋白-1在mRNA和蛋白水平的表达，表明肌成纤维细胞分化，并在研究过程中持续（2周）。这些研究证明了这种MMP可降解系统用于表征VIC的实用性、灵活性和生物活性，VIC是组织工程可行瓣膜置换和理解瓣膜病理学的重要细胞群。
Valvular interstitial cells (VICs) maintain functional heart valve structure and display transient fibroblast and myofibroblast properties. Most cell characterization studies have been performed on plastic dishes; while insightful, these systems are limited. Thus, a matrix metalloproteinase (MMP) degradable poly(ethylene glycol) (PEG) hydrogel system is proposed in this communication as a useful tool for characterizing VIC function in 3D. When encapsulated, VICs attained spread morphology, and proliferated and migrated as shown through real-time cell microscopy. Additionally, fibronectin derived pendant RGD was incorporated into the system to promote integrin binding. As RGD concentration increased from 0 to 2000 μM, VIC process extension and integrinαvβ3 binding increased within two days. By day 10, integrin binding was equalized between conditions. VIC morphology and rate of process extension were also increased through decreasing the hydrogel matrix density presented to the cells. VIC differentiation in response to exogenously delivered transforming growth factor-beta1 (TGF-β1) was also examined within the hydrogel networks. TGF-β1 increased expression of alpha smooth muscle actin (αSMA) and collagen-1 at both the mRNA and protein level by day 2 of culture, indicating myofibroblast differentiation, and was sustained over the course of the study (2 weeks). These studies demonstrate the utility, flexibility, and biological activity of this MMP-degradable system for the characterization of VICs, an important cell population for tissue engineering viable valve replacements and understanding valvular pathobiology.
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影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
DOI：
10.1073/pnas.0737381100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Lutolf, MP;Lauer-Fields, JL;Hubbell, JA
通讯作者：
Hubbell, JA
影响因子：
--
作者：
Benton JA;DeForest CA;Vivekanandan V;Anseth KS
通讯作者：
Anseth KS
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：
4.8
作者：
Cushing, Melinda C.;Mariner, Peter D.;Liao, Jo-Tsu;Sims, Evan A.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.