Preprint Article Version 2 This version is not peer-reviewed

A Versatile Microfluidic Device System that Lacks a Synthetic Extracellular Matrix Recapitulates the Blood-Brain Barrier and Dynamic Tumor Cell Interaction

Version 1 : Received: 7 January 2024 / Approved: 8 January 2024 / Online: 8 January 2024 (11:27:33 CET)
Version 2 : Received: 11 October 2024 / Approved: 11 October 2024 / Online: 11 October 2024 (11:58:21 CEST)

How to cite: Santillán-Cortez, D.; Castell-Rodríguez, A. E.; González-Arenas, A.; Suarez-Cuenca, J. A.; Pérez-Koldenkova, V.; Añorve-Bailón, D.; García, S.; Toledo Lozano, C. G.; Escamilla-Tilch, M.; Mondragón-Terán, P. A Versatile Microfluidic Device System that Lacks a Synthetic Extracellular Matrix Recapitulates the Blood-Brain Barrier and Dynamic Tumor Cell Interaction. Preprints 2024, 2024010547. https://doi.org/10.20944/preprints202401.0547.v2 Santillán-Cortez, D.; Castell-Rodríguez, A. E.; González-Arenas, A.; Suarez-Cuenca, J. A.; Pérez-Koldenkova, V.; Añorve-Bailón, D.; García, S.; Toledo Lozano, C. G.; Escamilla-Tilch, M.; Mondragón-Terán, P. A Versatile Microfluidic Device System that Lacks a Synthetic Extracellular Matrix Recapitulates the Blood-Brain Barrier and Dynamic Tumor Cell Interaction. Preprints 2024, 2024010547. https://doi.org/10.20944/preprints202401.0547.v2

Abstract

Microfluidic systems offer controlled microenvironments for cell-to-cell and cell-to-stromainteractions, which have precise physiological, biochemical, and mechanical features. The opti-mization of their conditions to best resemble tumor microenvironments constitutes an experimentalmodeling challenge, particularly regarding carcinogenesis in the central nervous system (CNS), giventhe specific features of the blood–brain barrier (BBB). Gel-free 3D microfluidic cell culture systems(gel-free 3D-mFCCSs), including features such as self-production of extracellular matrices, providesignificant benefits, including promoting cell–cell communication, interaction, and cell polarity. Theproposed microfluidic system consisted of a gel-free culture device inoculated with human brainmicrovascular endothelial cells (HBEC5i), glioblastoma multiforme cells (U87MG), and astrocytes(ScienCell 1800). The gel-free 3D-mFCCS showed a diffusion coefficient of 4.06 × 109 m2·s1, and itreconstructed several features and functional properties that occur at the BBB, such as the vasculo-genic ability of HBEC5i and the high duplication rate of U87MG. The optimized conditions of thegel-free 3D-mFCCS allowed for the determination of cellular proliferation, invasion, and migration,with evidence of both physical and biochemical cellular interactions, as well as the production ofpro-inflammatory cytokines. In conclusion, the proposed gel-free 3D-mFCCSs represent a versatileand suitable alternative to microfluidic systems, replicating several features that occur within tumormicroenvironments in the CNS. This research contributes to the characterization of microfluidicapproaches and could lead to a better understanding of tumor biology and the eventual developmentof personalized therapies. (PDF) A Versatile Microfluidic Device System that Lacks a Synthetic Extracellular Matrix Recapitulates the Blood-Brain Barrier and Dynamic Tumor Cell Interaction. Available from: https://www.researchgate.net/publication/384802118_A_Versatile_Microfluidic_Device_System_that_Lacks_a_Synthetic_Extracellular_Matrix_Recapitulates_the_Blood-Brain_Barrier_and_Dynamic_Tumor_Cell_Interaction#fullTextFileContent [accessed Oct 10 2024].

Keywords

microfluidic system; glioblastoma; tumoral biology; organoid culture

Subject

Biology and Life Sciences, Biology and Biotechnology

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