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重建人类组织屏障功能,实现精准和个性化医学。

Reconstitution of human tissue barrier function for precision and personalized medicine.

机构信息

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.

出版信息

Lab Chip. 2024 Jul 10;24(14):3347-3366. doi: 10.1039/d4lc00104d.

Abstract

Tissue barriers in a body, well known as tissue-to-tissue interfaces represented by endothelium of the blood vessels or epithelium of organs, are essential for maintaining physiological homeostasis by regulating molecular and cellular transports. It is crucial for predicting drug response to understand physiology of tissue barriers through which drugs are absorbed, distributed, metabolized and excreted. Since the FDA Modernization Act 2.0, which prompts the inception of alternative technologies for animal models, tissue barrier chips, one of the applications of organ-on-a-chip or microphysiological system (MPS), have only recently been utilized in the context of drug development. Recent advancements in stem cell technology have brightened the prospects for the application of tissue barrier chips in personalized medicine. In past decade, designing and engineering these microfluidic devices, and demonstrating the ability to reconstitute tissue functions were main focus of this field. However, the field is now advancing to the next level of challenges: validating their utility in drug evaluation and creating personalized models using patient-derived cells. In this review, we briefly introduce key design parameters to develop functional tissue barrier chip, explore the remarkable recent progress in the field of tissue barrier chips and discuss future perspectives on realizing personalized medicine through the utilization of tissue barrier chips.

摘要

人体中的组织屏障,如血管内皮或器官上皮等组织-组织界面,是维持生理内稳态的关键,它们通过调节分子和细胞转运来实现这一功能。为了预测药物反应,了解药物吸收、分布、代谢和排泄所经过的组织屏障的生理学特性至关重要。自美国食品药品监督管理局(FDA)现代化法案 2.0 推动替代动物模型技术的出现以来,组织屏障芯片作为器官芯片或微生理系统(MPS)的应用之一,最近才被应用于药物开发领域。干细胞技术的最新进展为组织屏障芯片在个性化医疗中的应用带来了新的希望。在过去的十年中,设计和工程这些微流控设备,并展示其重新构建组织功能的能力一直是该领域的主要关注点。然而,该领域现在正在向更高的挑战迈进:验证它们在药物评估中的效用,并使用患者来源的细胞创建个性化模型。在这篇综述中,我们简要介绍了开发功能性组织屏障芯片的关键设计参数,探讨了组织屏障芯片领域的显著最新进展,并讨论了通过利用组织屏障芯片实现个性化医疗的未来展望。

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