基于细胞3D打印技术的肿瘤药物筛选细胞芯片研究

doi:10.3969/j.issn.0258-8021. 2014. 02.005

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摘要现有的药物筛选评价技术中，动物筛选模型存在种属差异和周期长等缺点，高通量筛选和细胞筛选模型则与体内环境差异大，药物筛选准确率低。细胞3D打印技术为在体外构建仿真的组织器官模型提供了可能，当其与细胞芯片技术结合则为体外构建高效准确的药物筛选模型提供了新的技术空间。本研究构建了含有多个叉指电极（IDEs）阵列的细胞芯片，用细胞3D打印技术在芯片上组装了卵巢癌细胞HO-8910和人肝间充质干细胞HMSC-H组织模型，并通过对组织模型内细胞阻抗变化的检测，反映细胞生长、贴附、增殖、凋亡的过程及药物对细胞活性的影响等，最终基于该模型检测了抗癌药物顺铂和环磷酰胺对肿瘤细胞的杀伤和肝毒性。结果显示：支架微丝直径和孔径约为200～300 μm，肿瘤细胞和肝细胞在三维结构里生长良好；DMEM作为电解液，芯片在10.4 Hz可准确检测到三维结构中细胞增殖引起的阻抗变化，20 h后阻抗升高69.6%；基于该筛选模型，能同步检测到药物的抗肿瘤作用和肝毒性，并筛选出需要肝的二次代谢产物才能产生抗肿瘤性的药物环磷酰胺。

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	赵占盈徐铭恩^*石然郭淼严明徐莹王玲

关键词 ：细胞3D打印, 细胞芯片, 药物筛选, 叉指电极, 支架

Abstract：There are some crucial problems in conventional drug screening systems. For example, animal models have shortcomings of species differences and long test periods; in addition, poor mimics of in vivo microenvironment results in the low accuracy of cellbased highthroughput drug screening assays. The 3D cell printing technology may provide solutions of establishing biomimetic tissue models in vitro. Moreover, the combination of 3D cell printing and cell chip provides a highly valuable tool for the efficient and accurate drug screening in vitro. In this study, a cell chip integrating several groups of IDEs, was designed and manufactured. Then, the HMSCH and HO-8910 cell lines were assembled within the gelatin/alginate mixture on the manufactured chip using 3D cell printing. The IDEs was used to detect changes in the cell impedance which reflects the cell growth, adhesion, proliferation, apoptosis and effects of drugs on the viability. Based on this cellsloaded chip, the antitumor effect or hepatoxicity of both CTX and DDP were measured respectively. Our results showed that the 3D structure could suppot the growth of HMSC-H or HO-8910 cells. The scaffold possessed pores with diameter of 200-300 μm. The change of impedance caused by the cell proliferation was precisely detected by the chip at 10.4 Hz using DMEM as electrolyte solution, 20 h later, the cell impedance increased by 69.6%. Using this chipbased in vitro drug screening model, we simultaneously detected the antitumor effect and hepatotoxicity of the drugs. Meanwhile, the efficacy of these drugs, which require hepatic metabolism for activation such as CTX, was also evaluated in the same chip.

Key words： 3D cell printing cell chip drug screening IDEs scaffold

基金资助:国家自然科学基金（81371695, 61108083)；浙江省科技计划（2011C23031）

引用本文:

赵占盈徐铭恩^*石然郭淼严明徐莹王玲. 基于细胞3D打印技术的肿瘤药物筛选细胞芯片研究[J]. 中国生物医学工程学报, 2014, 33(2): 161-169.
ZHAO Zhan Ying XU MingEn^* SHI Ran GUO Miao YAN Ming XU Ying WANG Ling. Research of AntiTumor Drug Screening Cell Chip Based on 3D Cell Printing Technique. journal1, 2014, 33(2): 161-169.

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http://cjbme.csbme.org/CN/10.3969/j.issn.0258-8021. 2014. 02.005 或 http://cjbme.csbme.org/CN/Y2014/V33/I2/161

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