Interaction among a three-dimensional scaffold, vessels and cells in the culture of tumor cells

doi:10.3969/j.issn.2095-4344.2013.42.016

Abstract

Abstract:

BACKGROUND: The tumor tissue engineering can build an integrated culture model to fully simulate the in vivo microenvironment of tumor growth, which can be used to study tumor developmental dynamics and related treatment strategies.
OBJECTIVE: To review the three-dimensional culture of tumor cells using tumor engineering technology.
METHODS: PubMed database was retrieved for articles related to tumor engineering, three-dimensional culture of tumor cells, biological scaffold materials and tumor microenvironment published from January 1992 to March 2013.
RESULTS AND CONCLUSION: Three-dimensional culture, because of its reproducible tissue and cell growth in vivo, has become an important platform for study of tumor resistance, invasiveness and tumor microenvironment. The three-dimensional culture has showed a trend to gradually replace the flat culture technique in many fields, and provides a research platform which is very close to in vivo environment. In recent years, with the development of tumor engineering, a variety of new polymer materials have been used in the three-dimensional culture of tumor cells. Three-dimensional culture technology is becoming a hotspot in the field of tumor biology, in which, using a variety of methods and materials, the cells show a growth in the spatial manner to form a biological support or matrix similar to in vivo growth environment. Biomaterials have become the soil on which seed cells can grow well, and plays an alternative to the extracellular matrix or the matrix of tissues and organs in the tumor engineering. Therefore, the three-dimensional cell culture has been widely used in cancer research, which has become a powerful tool to tumor drug resistance, angiogenesis, cell-cell interaction, signal transduction, stem cells and other research.

Key words: biocompatible materials, tumor cells, cultured, cell culture techniques, stents

CLC Number:

R318

Hu Xue-feng, Zheng Li, Zhao Jin-min. Interaction among a three-dimensional scaffold, vessels and cells in the culture of tumor cells[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(42): 7442-7448.

Figures/Tables 1

2.1 种子细胞三维培养种子细胞是肿瘤工程构建的核心，是肿瘤工程研究领域中的基础环节。首先用于三维培养的细胞需满足以下3个基本前提：①具有特定的分化表型或定向分化潜能。②可靠的细胞来源。③不引发移植排斥反应。基于这些原因，人类肿瘤细胞是首选对象。首先，肿瘤细胞在体内具有不受控增殖性，在体外培养中仍如此。肿瘤细胞形成集落(克隆)的能力比正常细胞强，另外增殖数量增多扩展时接触抑制消除，细胞能相互重叠向三维空间发展，形成堆积物。其次，永生性也称不死性，在体外培养中表现为细胞可无限传代而不凋亡，这有利于细胞的培养及收集。再次，肿瘤细胞在缺氧状态下高表达血管生成因子，提示肿瘤细胞在肿瘤发生和演进阶段有间接促血管生成作用[6]。有研究发现两种G蛋白联受体，甲酰化肽受体和趋化因子受体4是血管生成的重要介导分子[7]，这有利于肿瘤成活尤其利于应用组织工程构建体内肿瘤模型。第四，肿瘤细胞可合成一些多肽类生长因子，作用于自身相应的功能性受体，通过自分泌环路维持其增殖[8]。一些正性调控因子，如胰岛素样生长因子、白细胞介素6[9]、表皮生长因子等促进肿瘤细胞生长[10-11]。 2.2 土壤-生物支架材料生物材料就是种子细胞生长的土壤，在肿瘤工程中起着替代细胞外基质或组织、器官基质的作用。理想的肿瘤工程的支架材料具有以下特点：①无毒性，具有良好的生物组织相容性[12-13]，不引起机体的免疫排斥反应。②有一定孔隙率，良好的表面活性[14]，维持生长其上的细胞形态和表型，为三维生长的细胞提供支架，使细胞间形成适宜的空间分布。③具有生物可降解性，可塑性和一定的机械强度[14]。④能增进细胞的黏附和增殖[15-16]，诱导细胞定向分化。不同工程组织、器官的体外构建对生物材料生物活性的要求各不相同。目前，肿瘤细胞三维培养所用的生物材料众多，有细胞外基质、高分子聚合材料及有机材料复合物等。肿瘤细胞三维培养所用的生物材料："

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