将多细胞球体纳入 3D 聚合物支架中为筛选抗癌药物提供了一种改进的肿瘤模型。
Incorporation of multicellular spheroids into 3-D polymeric scaffolds provides an improved tumor model for screening anticancer drugs.
机构信息
Department of Bioengineering, University of California, Los Angeles, California, USA.
出版信息
Cancer Sci. 2010 Dec;101(12):2637-43. doi: 10.1111/j.1349-7006.2010.01723.x. Epub 2010 Sep 17.
Abstract
Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three-dimensional (3-D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3-D porous scaffolds. Drug resistance assays showed that spheroid-seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid-seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid-seeded 3-D scaffolds might serve as a useful in vitro system for screening cancer therapeutics.
摘要
癌症治疗药物的开发需要在动物试验和后续临床试验之前，对药物疗效进行彻底的体外评估。因此，人们研究了三维（3-D）体外模型来进行药物筛选。在本研究中，我们开发了一种新的体外模型，其中将细胞聚集体或球体嵌入 3-D 多孔支架中。药物耐药性测定表明，与单层培养物、平面基底上的球体或接种离散细胞的支架相比，球体接种的支架具有更高的耐药性。此外，球体接种的支架表现出更高的乳酸产生导致酸中毒，并表现出更高的血管生成因子表达。这些数据表明，球体接种的 3-D 支架可能作为筛选癌症治疗药物的有用体外系统。
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