Microfluidic device for expedited tumor growth towards drug evaluation
Microfluidic device for expedited tumor growth towards drug evaluation
复制标题
用于加速肿瘤生长以进行药物评估的微流体装置
DOI：
10.1039/c8lc01250d
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Liu, Yaling
中科院分区：
文献类型：
--
作者：
Uhl, Christopher George;Liu, Yaling
患者来源的类器官已经成为筛选抗癌治疗剂的稳健的临床前模型。目前的2D培养方法不提供对治疗的生理反应，因此正在开发3D模型以更好地再现生理反应。然而，3D培养通常需要大量的初始细胞群和一周到一个月的时间来生长肿瘤，为治疗测试做好准备。作为一种解决方案，已经开发了一种3D培养系统，该系统能够以快速的方式产生生理相关的肿瘤，同时仅需要少量的初始癌细胞。能够促进对癌细胞群体的主动对流营养供应的双层微流体系统在从小至8个细胞的群体开始时促进癌细胞的加速生长。该系统已被证明能很好地与粘附和非粘附细胞类型的功能，通过加速细胞生长的一个因素，范围从1.27至4.76大于在静态条件下的生长。利用这种方法能够在3天内形成准备好进行治疗筛选的肿瘤，并且证明了在微流体系统内进行治疗筛选的能力。已经开发了一种数学模型，该模型允许对营养物的动态输送进行调整，以便有效地使用培养基而不产生过多的浪费。我们相信这项工作是第一次尝试在微流体系统内仅利用对流营养供应以加速方式生长癌症，这也有助于设备上的治疗筛选。开发的微流体系统和癌症生长方法有可能为临床环境中的患者提供改进的药物筛选。
Patient derived organoids have emerged as robust preclinical models for screening anti-cancer therapeutics. Current 2D culturing methods do not provide physiological responses to therapeutics, therefore 3D models are being developed to better reproduce physiological responses. 3D culturing however often requires large initial cell populations and one week to one month to grow tumors ready for therapeutic testing. As a solution a 3D culturing system has been developed capable of producing physiologically relevant tumors in an expedited fashion while only requiring a small number of initial cancer cells. A bi-layer microfluidic system capable of facilitating active convective nutrient supply to populations of cancer cells facilitates expedited growth of cancer cells when starting with populations as small as 8 cells. The system has been shown to function well with adherent and non-adherent cell types by expediting cell growth by a factor ranging from 1.27 to 4.76 greater than growth under static conditions. Utilizing such an approach has enable to formation of tumors ready for therapeutic screening within 3 days and the ability to perform therapeutic screening within the microfluidic system is demonstrated. A mathematical model has been developed which allows for adjustments to be made to the dynamic delivery of nutrients in order to efficiently use culture media without excessive waste. We believe this work to be the first attempt to grow cancers in an expedited fashion utilizing only a convective nutrient supply within a microfluidic system which also facilitates on-device therapeutic screening. The developed microfluidic system and cancer growth method have the potential to offer improved drug screening for patients in clinical settings.