Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance.
Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance.
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DOI：
10.1007/s11095-010-0198-3
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发表时间：
2010-09
影响因子：
3.7
通讯作者：
Zhang, Miqin
中科院分区：
文献类型：
--
作者：
Leung, Matthew;Kievit, Forrest M.;Florczyk, Stephen J.;Veiseh, Omid;Wu, Jennifer;Park, James O.;Zhang, Miqin
肝细胞癌是一种常见的实体恶性肿瘤。由于缺乏能够有效代表体内肿瘤微环境的体外细胞培养系统，迫切需要的新疗法的发现一直受到阻碍。为了满足这一需求，利用生物相容性的壳聚糖-海藻酸盐(CA)支架与人肝癌细胞系培养，开发了一种3D体外肝癌模型。研究肿瘤生长因子的分泌、细胞外基质的产生等细胞功能与体内肿瘤生长及血管募集的关系。生长在3D CA支架上的肝癌细胞表现出形态特征和高度恶性细胞标志物的表达增加。与人肝癌细胞共培养的CA支架植入小鼠体内，肿瘤生长明显加快。组织学显示，不同预培养条件产生的肿瘤在形态和新形成的血管组织上存在显著差异。与2D或Matrigel培养的肝癌细胞相比，CA支架培养的肝癌细胞对阿霉素的耐药性显著。这种肝细胞癌的三维模型能够更接近地模拟体内的肿瘤行为，为研究和应用新的抗癌治疗药物提供了一个宝贵的模型。
Hepatocellular carcinoma (HCC) is a prevalent solid malignancy. Critically needed discovery of new therapeutics has been hindered by lack of an in vitro cell culture system that can effectively represent the in vivo tumor microenvironment. To address this need, a 3D in vitro HCC model was developed using a biocompatible, chitosan-alginate (CA) scaffold cultured with the human HCC cell lines. The correlation between the cell function such as secretion of growth factors and production of ECM in vitro, and the tumor growth and blood vessel recruitment in vivo was investigated. HCC cells grown on 3D CA scaffolds demonstrated morphology characteristic and increased expression of markers of highly malignant cells. Implantation of CA scaffolds cultured with human HCC cells in mice showed accelerated tumor growth. Histology revealed marked differences in morphology and organization of newly formed blood vessels between tumors produced by different pre-cultured conditions. Resistance to doxorubicin was significantly pronounced in CA scaffold-cultured HCC cells compared to 2D or Matrigel cultured HCC cells. This 3D model of HCC, with its ability to more closely mimic the in vivo tumor behavior, may serve as an invaluable model for study and application of novel anticancer therapeutics against HCC.
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DOI：
10.1089/ten.teb.2009.0270
发表时间：
2009-09
期刊：
Tissue engineering. Part B, Reviews
影响因子：
--
作者：
Lund AW;Yener B;Stegemann JP;Plopper GE
通讯作者：
Plopper GE
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
6.4
作者：
Chau, Y;Padera, RF;Langer, R
通讯作者：
Langer, R
影响因子：
13.5
作者：
Lai, Jin-Ping;Sandhu, Dalbir S.;Roberts, Lewis R.
通讯作者：
Roberts, Lewis R.
影响因子：
48
作者：
Fischbach, Claudia;Chen, Ruth;Mooney, David J.
通讯作者：
Mooney, David J.