Construction of a novel blood brain barrier-glioma microfluidic chip model: Applications in the evaluation of permeability and anti-glioma activity of traditional Chinese medicine components.
Construction of a novel blood brain barrier-glioma microfluidic chip model: Applications in the evaluation of permeability and anti-glioma activity of traditional Chinese medicine components.
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DOI：
10.1016/j.talanta.2022.123971
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发表时间：
2022-09
期刊：
影响因子：
6.1
通讯作者：
Yiwei Shi;Xiaoli He;Hui Wang;Jianying Dai;Jiahao Fang;Yuzhen He;Xiaofei Chen;Z. Hong;Y. Chai
中科院分区：
文献类型：
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作者：
Yiwei Shi;Xiaoli He;Hui Wang;Jianying Dai;Jiahao Fang;Yuzhen He;Xiaofei Chen;Z. Hong;Y. Chai
由于大多数抗胶质瘤候选药物难以透过血脑屏障（BBB），因此迫切需要能够整合肿瘤微环境的复杂性和BBB的结构和功能的临床前模型用于治疗胶质瘤。在此，我们构建了一个由原代人脑微血管内皮细胞、周细胞、星形胶质细胞和胶质瘤细胞组成的体外血脑屏障-胶质瘤微流控芯片模型，该模型能够再现人血脑屏障和胶质瘤微环境的高水平屏障功能。BBB-胶质瘤微流控芯片（BBB-U251芯片）中的BBB单元对不同分子量的异硫氰酸荧光素异构体-葡聚糖（FITC-dextran）和3种不同透过行为的模型药物具有选择性透过性，表明该胶质瘤模型存在功能性屏障。采用高效液相色谱-紫外联用技术（HPLC-UV），对6种具有抗胶质瘤活性的中药成分进行了血透量的测定。然后将渗透药物直接作用于三维培养的胶质瘤细胞（U251），以评价药物疗效。药物渗透系数的计算结果与传统Transwell模型的体内数据更为接近。由于血脑屏障的存在，血脑屏障-U251芯片中药物对U251细胞的作用明显降低。脑胶质瘤的药物反应表明，在开发抗脑胶质瘤新药时，有必要考虑BBB。因此，这种集成了BBB功能的3D胶质瘤微流体模型可以成为筛选脑肿瘤抗癌药物的有用平台。
Since most anti-glioma drug candidates hardly permeate through the blood-brain barrier (BBB), preclinical models that can integrate the complexity of the tumor microenvironment and the structure and function of the BBB is urgently needed for the treatment of glioma. Herein, we constructed anin vitroBBB-glioma microfluidic chip model lined by primary human brain microvascular endothelial cells, pericytes, astrocytes and glioma cells, which could recapitulate the high level of barrier function of thein vivohuman BBB and glioma microenvironment. The BBB unit in BBB-glioma microfluidic chip (BBB–U251 chip) displayed selective permeability to fluorescein isothiocyanate isomer-dextran (FITC-dextran) with different molecular weights and three model drugs with different permeability behavior across BBB, which indicated that this glioma model included a functional barrier. Six potential anti-glioma components in traditional Chinese medicine (TCM) were delivered into the blood channel and the permeated amount was quantified by high-performance liquid chromatography combined with ultraviolet (HPLC-UV). The permeated drugs then directly acted on 3D cultured glioma cells (U251) to evaluate the drug efficacy. The results of permeability coefficients of drugs showed that the data were closer to thein vivodata of traditional Transwell model. The effect of the drugs on U251 cells in the BBB-U251 chip was significantly lower due to the existence of BBB. Drug responses on glioma demonstrated the necessity to take BBB into account during the development of anti-glioma new drugs. Therefore, this 3D glioma microfluidic models integrating the BBB functionality can be a useful platform for screening the anticancer drug for brain tumors.