Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials,Lab on a Chip

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Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials
Lab on a Chip ( IF 6.1 ) Pub Date : 2020-10-26 , DOI: 10.1039/d0lc00252f
María Virumbrales-Muñoz ₁ , Jiong Chen , Jose Ayuso , Moonhee Lee , E Jason Abel , David J Beebe

Affiliation

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer associated with the development of abnormal tumor angiogenesis. Although multiple anti-angiogenic therapies have been developed, responses to individual treatment are highly variable between patients. Thus, the use of one-patient clinical trials has been suggested as an alternative to standard trials. We used a microfluidic device to generate organotypic primary patient-specific blood vessel models using normal (NEnC) and tumor-associated primary CD31⁺ selected cells (TEnC). Our model was able to recapitulate differences in angiogenic sprouting and vessel permeability that characterize normal and tumor-associated vessels. We analyzed the expression profile of vessel models to define vascular normalization in a patient-specific manner. Using this data, we identified actionable targets to normalize TEnC vessel function to a more NEnC-like phenotype. Finally, we tested two of these drugs in our patient-specific models to determine the efficiency in restoring vessel function showing the potential of the model for single-patient clinical trials.

中文翻译：

用于单患者临床试验的透明细胞肾细胞癌器官型原代血管模型

透明细胞肾细胞癌（ccRCC）是一种常见的泌尿生殖系统癌症，与异常肿瘤血管生成的发展相关。尽管已经开发出多种抗血管生成疗法，但患者对个体治疗的反应差异很大。因此，有人建议使用单患者临床试验作为标准试验的替代方案。我们使用微流体装置使用正常 (NEnC) 和肿瘤相关原代 CD31 ⁺选择细胞 (TEnC) 生成器官型原代患者特异性血管模型。我们的模型能够概括正常血管和肿瘤相关血管特征的血管生成萌芽和血管通透性的差异。我们分析了血管模型的表达谱，以针对患者特定的方式定义血管正常化。利用这些数据，我们确定了可操作的目标，将 TEnC 血管功能标准化为更像 NEnC 的表型。最后，我们在患者特异性模型中测试了其中两种药物，以确定恢复血管功能的效率，显示该模型在单患者临床试验中的潜力。

更新日期：2020-11-03

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