Engineered smooth muscle tissues: Regulating cell phenotype with the scaffold
Engineered smooth muscle tissues: Regulating cell phenotype with the scaffold
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DOI：
10.1006/excr.1999.4595
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发表时间：
1999-09-15
影响因子：
3.7
通讯作者：
Mooney, DJ
中科院分区：
文献类型：
--
作者：
Kim, BS;Nikolovski, J;Mooney, DJ
在三维可生物降解的支架上培养细胞可以产生适合于重建手术应用或作为新型体外模型系统的组织。在这项研究中，我们已经测试的假设，即平滑肌细胞（SMC）在三维，工程组织的表型是由支架材料的化学调节。具体地说，我们直接比较了细胞生长和细胞外基质（ECM）的模式（例如，弹性蛋白和胶原蛋白）基因在两种类型的合成聚合物支架和I型胶原蛋白支架上的表达。SMC在合成聚合物支架上的生长速率显著高于I型胶原海绵。在培养的第11天，在聚乙醇酸（PGA）支架上的SMC产生弹性蛋白的速率比在I型胶原海绵上的高3.5 +/-1.1倍。相比之下，I型胶原海绵上的胶原产生速率比PGA支架上的胶原产生速率高3.3 +/-1.1倍。北方印迹分析证实了弹性蛋白和胶原蛋白基因表达之间的这种支架依赖性转换。通过在支架材料的二维膜上培养SMC，证实了支架化学调节SMC表型与支架物理形式无关的发现。很可能细胞通过不同的配体粘附到这些支架上，因为从血清吸附到合成聚合物上的主要蛋白质是玻连蛋白，而纤连蛋白和玻连蛋白以高密度存在于I型胶原海绵上。总之，本研究表明，三维平滑肌样组织可以通过在三维支架上培养SMC来产生，并且SMC的表型受到支架化学的强烈调控。这些工程化组织提供了新的三维模型来研究细胞与ECM的体外相互作用。(C)北京：科学出版社.
Culturing cells on three-dimensional, biodegradable scaffolds may create tissues suitable either for reconstructive surgery applications or as novel in vitro model systems. In this study, we have tested the hypothesis that the phenotype of smooth muscle cells (SMCs) in three-dimensional, engineered tissues is regulated by the chemistry of the scaffold material. Specifically, we have directly compared cell growth and patterns of extracellular matrix (ECM) (e.g., elastin and collagen) gene expression on two types of synthetic polymer scaffolds and type I collagen scaffolds. The growth rates of SMCs on the synthetic polymer scaffolds were significantly higher than on type I collagen sponges. The rate of elastin production by SMCs on polyglycolic acid (PGA) scaffolds was 3.5 +/- 1.1-fold higher than that on type I collagen sponges on Day 11 of culture. In contrast, the collagen production rate on type I collagen sponges was 3.3 +/- 1.1-fold higher than that on PGA scaffolds. This scaffold-dependent switching between elastin and collagen gene expression was confirmed by Northern blot analysis. The finding that the scaffold chemistry regulates the phenotype of SMCs independent of the scaffold physical form was confirmed by culturing SMCs on two-dimensional films of the scaffold materials. It is likely that cells adhere to these scaffolds via different ligands, as the major protein adsorbed from the serum onto synthetic polymers was vitronectin, whereas fibronectin and vitronectin were present at high density on type I collagen sponges. In summary, this study demonstrates that three-dimensional smooth muscle-like tissues can be created by culturing SMCs on three-dimensional scaffolds, and that the phenotype of the SMCs is strongly regulated by the scaffold chemistry, These engineered tissues provide novel, three-dimensional models to study cellular interaction with ECM in vitro. (C) 1999 Academic Press.