James A Haley VA Hospital, Tampa, FL, USA; Center for Research and Education in Nanobioengineering, Department of Internal Medicine and Pharmacy Graduate Programs, University of South Florida, Tampa, FL, USA.
Center for Research and Education in Nanobioengineering, Department of Internal Medicine and Pharmacy Graduate Programs, University of South Florida, Tampa, FL, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
Nanomedicine. 2020 Nov;30:102294. doi: 10.1016/j.nano.2020.102294. Epub 2020 Aug 26.
The tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and drug resistance. However, models recapitulating the complex 3D structure, heterogeneous cell environment, and cell-cell interactions found in vivo are lacking. Herein, we report on a gravitational microfluidic platform (GMP) retrofitted with MEMS sensors, which is integrated with 3D nanofiber scaffold-aided tumoroid culture. The results showed that this GMP for tumoroid growth mimics the tumor microenvironment more precisely than static culture models of colon cancer, including higher drug resistance, enhanced cancer stem cell properties, and increased secretion of pro-tumor cytokines. In addition, the GMP includes an integrated surface acoustic wave-based biosensing to monitor cell growth and pH changes to assess drug efficacy. Thus, this simple-to-use perfused GMP tumoroid culture system for in vitro and ex vivo studies may accelerate the drug development process and be a tool in personalized cancer treatment.
肿瘤微环境在肿瘤的发生、发展、转移和耐药中起着关键作用。然而，目前缺乏能够重现体内复杂的 3D 结构、异质细胞环境和细胞-细胞相互作用的模型。在这里，我们报告了一个经过改装的带有 MEMS 传感器的重力微流控平台（GMP），它与 3D 纳米纤维支架辅助的类器官培养相结合。结果表明，与结肠癌的静态培养模型相比，这种用于类器官生长的 GMP 更能精确模拟肿瘤微环境，包括更高的耐药性、增强的癌症干细胞特性和增加的促肿瘤细胞因子分泌。此外，GMP 还包括一个集成的基于表面声波的生物传感，以监测细胞生长和 pH 值变化，从而评估药物疗效。因此，这种用于体外和离体研究的简单易用的灌注 GMP 类器官培养系统可能会加速药物开发过程，并成为个性化癌症治疗的工具。
