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Open multi-culture platform for simple and flexible study of multi-cell type interactions†
Lab on a Chip ( IF 6.1 ) Pub Date : 2018-09-11 00:00:00 , DOI: 10.1039/c8lc00560e
Yasmín R Álvarez-García 1 , Karla P Ramos-Cruz , Reinaldo J Agostini-Infanzón , Loren E Stallcop , David J Beebe , Jay W Warrick , Maribella Domenech
Affiliation  

The study of multi-cell-type (MCT) interactions has the potential to significantly impact our understanding of tissue and disease biology. Such studies require innovative culture tools for unraveling the contributions of each cell type. Micro- and macro-scale platforms for MCT culture each have different advantages and disadvantages owing to their widely different capabilities, availability, and ease-of-use. However, as evidenced in the literature, there are very few examples of MCT studies and culture platforms, suggesting both biological and technical barriers. We have developed an open multi-culture platform to promote more rapid progress by integrating advantages of both micro- and macro-scale culture devices. The proposed open multi-culture platform addresses technical barriers by allowing easy customization, independent control of basic physical culture parameters, and incorporation of multiple culture modalities (e.g., 2D, 3D, transwell, and spheroid). The design also permits the user to obtain independent endpoints for each culture region. We demonstrate use of the platform in two example studies where we evaluated how cell ratio and cell types influence the response of triple negative breast cancer cells to heat damage and Hedgehog signaling. We also show that the platform can improve soluble factor transport between cell types compared to compartmentalized macro- and micro-scale alternatives. Last, we examine current and future challenges of the platform. We envision simple, yet flexible and customizable, platforms such as this will be important for advancing in vitro study of tissue and tumor biology.

中文翻译:

开放的多培养平台,用于简单灵活地研究多细胞类型的相互作用†

多细胞类型 (MCT) 相互作用的研究有可能显着影响我们对组织和疾病生物学的理解。此类研究需要创新的培养工具来揭示每种细胞类型的贡献。MCT 文化的微观和宏观平台各有不同的优点和缺点,因为它们的功能、可用性和易用性大相径庭。然而,正如文献所证明的,MCT 研究和培养平台的例子很少,这表明生物和技术障碍。我们开发了一个开放的多元文化平台,通过整合微观和宏观培养设备的优势,促进更快的进步。提议的开放式多元文化平台通过允许轻松定制来解决技术障碍,例如,2D、3D、transwell 和球体)。该设计还允许用户获得每个培养区域的独立端点。我们在两个示例研究中展示了该平台的使用,其中我们评估了细胞比率和细胞类型如何影响三阴性乳腺癌细胞对热损伤和 Hedgehog 信号传导的反应。我们还表明,与划分的宏观和微观尺度替代方案相比,该平台可以改善细胞类型之间的可溶性因子转运。最后,我们研究了该平台当前和未来的挑战。我们设想这样的简单、灵活和可定制的平台对于推进组织和肿瘤生物学的体外研究非常重要。
更新日期:2018-09-11
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