Engineering a High-Throughput 3-D In Vitro Glioblastoma Model.
Engineering a High-Throughput 3-D In Vitro Glioblastoma Model.
复制标题
建立高通量三维体外胶质母细胞瘤模型
DOI：
10.1109/jtehm.2015.2410277
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发表时间：
2015
影响因子：
3.4
通讯作者：
Akay M
中科院分区：
文献类型：
--
作者：
Fan Y;Avci NG;Nguyen DT;Dragomir A;Akay YM;Xu F;Akay M
由于其高度侵袭性，多形性胶质母细胞瘤（GBM）是成人中最常见和最恶性的原发性脑肿瘤。GBM的现有治疗包括切除、化疗和放疗的组合，其成功率非常有限，中位生存率<1年。这主要是因为未能及早发现和有效治疗。我们设计了一种新型的基于微孔的三维GBM细胞培养模型，该模型可以模拟体外环境，并有助于绕过缺乏合适的动物模型进行临床前毒性试验。微孔由简单且廉价的聚乙二醇材料制成，用于控制体外3-D培养。我们将三维微图案化系统应用于GBM（U-87）细胞，使用光刻技术来控制细胞球体的形状、尺寸和厚度。我们的初步结果表明，可以在三维中形成均匀的GBM球状体，并且这些GBM球状体的大小取决于微孔的大小。以这种方式产生的球状体的活力使用活/死测定法定量评估，并显示在21天内改善。我们相信，体外三维细胞培养模型可以帮助减少临床前脑肿瘤生长研究的时间。所提出的新平台对于癌症药物的高通量筛选和治疗反应的评估可能是有用的和具有成本效益的。多形性胶质母细胞瘤（GBM）是成人中最常见和最恶性的原发性脑肿瘤。GBM的现有治疗方法包括切除、化疗和放疗，其成功率非常有限，中位生存率不到1年，主要原因是未能早期发现和有效治疗。我们提出了一种基于微孔的新型3D GBM细胞培养模型，该模型可以模拟体内环境，并有助于绕过缺乏合适的动物模型进行临床前毒性试验。微孔由简单且廉价的PEG材料制成，用于控制体外3D培养。以这种方式产生的球状体的活力使用活/死测定法定量评估，并显示在21天内改善。所提出的新平台对于癌症药物的高通量筛选和治疗反应的评估可能是有用的和具有成本效益的。
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults because of its highly invasive behavior. The existing treatment for GBM, which involves a combination of resection, chemotherapy, and radiotherapy, has a very limited success rate with a median survival rate of <1 year. This is mainly because of the failure of early detection and effective treatment. We designed a novel 3-D GBM cell culture model based on microwells that could mimic in vitro environment and help to bypass the lack of suitable animal models for preclinical toxicity tests. Microwells were fabricated from simple and inexpensive polyethylene glycol material for the control of in vitro 3-D culture. We applied the 3-D micropatterning system to GBM (U-87) cells using the photolithography technique to control the cell spheroids’ shape, size, and thickness. Our preliminary results suggested that uniform GBM spheroids can be formed in 3-D, and the size of these GBM spheroids depends on the size of microwells. The viability of the spheroids generated in this manner was quantitatively evaluated using live/dead assay and shown to improve over 21 days. We believe that in vitro 3-D cell culture model could help to reduce the time of the preclinical brain tumor growth studies. The proposed novel platform could be useful and cost-effective for high-throughput screening of cancer drugs and assessment of treatment responses. Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. The existing treatment for GBM, which involves a combination of resection, chemotherapy and radiotherapy, has a very limited success rate with a median survival rate of less than 1 year, mainly because of the failure of early detection and effective treatment. We present a novel 3D GBM cell culture model based on microwells that could mimic the in vivo environment and help to bypass the lack of suitable animal models for preclinical toxicity tests. Microwells were fabricated from simple and inexpensive PEG material for the control of in vitro 3D culture. The viability of the spheroids generated in this manner was quantitatively evaluated using live/dead assay and shown to improve over 21 days. The proposed novel platform could be useful and cost-effective for high-throughput screening of cancer drugs and assessment of treatment responses.