Department of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY, 14853, USA.
Biomed Microdevices. 2013 Aug;15(4):583-593. doi: 10.1007/s10544-013-9763-y.
Prevailing evidence has established the fundamental role of microenvironmental conditions in tumorigenesis. However, the ability to identify, interrupt, and translate the underlying cellular and molecular mechanisms into meaningful therapies remains limited, due in part to a lack of organotypic culture systems that accurately recapitulate tumor physiology. Integration of tissue engineering with microfabrication technologies has the potential to address this challenge and mimic tumor heterogeneity with pathological fidelity. Specifically, this approach allows recapitulating global changes of tissue-level phenomena, while also controlling microscale variability of various conditions including spatiotemporal presentation of soluble signals, biochemical and physical characteristics of the extracellular matrix, and cellular composition. Such platforms have continued to elucidate the role of the microenvironment in cancer pathogenesis and significantly improve drug discovery and screening, particularly for therapies that target tumor-enabling stromal components. This review discusses some of the landmark efforts in the field of micro-tumor engineering with a particular emphasis on deregulated tissue organization and mass transport phenomena in the tumor microenvironment.
现有证据已经确立了微环境条件在肿瘤发生中的基本作用。然而,由于缺乏能够准确再现肿瘤生理学的器官型培养系统,将潜在的细胞和分子机制识别、中断和转化为有意义的治疗方法的能力仍然有限。组织工程与微制造技术的结合有可能解决这一挑战,并以病理保真度模拟肿瘤异质性。具体来说,这种方法允许重现组织水平现象的全局变化,同时控制各种条件的微尺度可变性,包括可溶性信号的时空呈现、细胞外基质的生化和物理特性以及细胞组成。这些平台继续阐明微环境在癌症发病机制中的作用,并极大地改善药物发现和筛选,特别是针对靶向肿瘤支持性基质成分的治疗方法。本文讨论了微肿瘤工程领域的一些具有里程碑意义的研究成果,特别强调了肿瘤微环境中组织失调和质量传输现象。