High Throughput, Polymeric Aqueous Two-Phase Printing of Tumor Spheroids.
High Throughput, Polymeric Aqueous Two-Phase Printing of Tumor Spheroids.
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DOI：
10.1002/adfm.201401302
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发表时间：
2014-11-05
影响因子：
19
通讯作者：
Tavana, Hossein
中科院分区：
文献类型：
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作者：
Atefi, Ehsan;Lemmo, Stephanie;Fyffe, Darcy;Luker, Gary D.;Tavana, Hossein
本文介绍了一种新的三维培养技术，用于高通量生产肿瘤球体，并验证了其筛选抗癌药物的实用性。我们使用两种不混溶的聚合物水溶液，并将含有细胞的“图案化”相的亚微升液滴微印到“浸没”相的浴中。使用一组生物相容性聚合物选择适当的双相系统制剂导致形成圆形液滴，其限制细胞以促进球状体的自发形成而无需任何外部刺激。使这种方法适应机器人工具使得能够在标准微孔板中直接生成和维持具有明确尺寸的球状体，并原位进行球状体的生化分析，这对于现有的球状体培养技术是不可能的。为了实现高通量筛选，我们建立了相图以鉴定特定体积的图案化液滴内的最小细胞密度，从而产生单个球状体。球状体在长期孵育中显示正常生长，并且当用药物化合物处理时细胞活力呈剂量依赖性降低，但与单层培养物相比呈现显著抗性。实施这种微技术的前所未有的容易性及其强大的性能将有利于利用生理相关的3D肿瘤模型对癌细胞进行药物筛选的高通量研究。
This paper presents a new 3D culture microtechnology for high throughput production of tumor spheroids and validates its utility for screening anti-cancer drugs. We use two immiscible polymeric aqueous solutions and microprint a submicroliter drop of the “patterning” phase containing cells into a bath of the “immersion” phase. Selecting proper formulations of biphasic systems using a panel of biocompatible polymers results in the formation of a round drop that confines cells to facilitate spontaneous formation of a spheroid without any external stimuli. Adapting this approach to robotic tools enables straightforward generation and maintenance of spheroids of well-defined size in standard microwell plates and biochemical analysis of spheroids in situ, which is not possible with existing techniques for spheroid culture. To enable high throughput screening, we establish a phase diagram to identify minimum cell densities within specific volumes of the patterning drop to result in a single spheroid. Spheroids show normal growth over long-term incubation and dose-dependent decrease in cellular viability when treated with drug compounds, but present significant resistance compared to monolayer cultures. The unprecedented ease of implementing this microtechnology and its robust performance will benefit high throughput studies of drug screening against cancer cells with physiologically-relevant 3D tumor models.
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影响因子：
3.8
作者：
Tibbitt, Mark W.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
DOI：
10.1016/j.jconrel.2012.04.045
发表时间：
2012-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Mehta G;Hsiao AY;Ingram M;Luker GD;Takayama S
通讯作者：
Takayama S
影响因子：
3.2
作者：
Das, Tamal;Meunier, Liliane;Mes-Masson, Anne-Marie
通讯作者：
Mes-Masson, Anne-Marie
影响因子：
14
作者：
Fukuda, Junji;Khademhosseini, Ali;Langer, Robert
通讯作者：
Langer, Robert
影响因子：
41.2
作者：
通讯作者：
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