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The Applications and Challenges of the Development of In Vitro Tumor Microenvironment Chips.

Authors
  • Johnson, Annika1
  • Reimer, Samuel1
  • Childres, Ryan1
  • Cupp, Grace1
  • Kohs, Tia C L2
  • McCarty, Owen J T2, 3
  • Kang, Youngbok Abraham1
  • 1 Department of Mechanical, Civil, and Biomedical Engineering, George Fox University, 414 N. Meridian Street, #6088, Newberg, OR 97132 USA.
  • 2 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239 USA.
  • 3 Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201 USA.
Type
Published Article
Journal
Cellular and molecular bioengineering
Publication Date
Feb 01, 2023
Volume
16
Issue
1
Pages
3–21
Identifiers
DOI: 10.1007/s12195-022-00755-7
PMID: 36660587
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create in vitro microfluidic models called "tumor chips". Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of in vitro tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies. © The Author(s) under exclusive licence to Biomedical Engineering Society 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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