Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells

Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Here, we have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a s...

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Main Authors: Sergei V. German, Anatolii A. Abalymov, Maxim A. Kurochkin, Yuliya Kan, Dmitry A. Gorin, Marina V. Novoselova
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/4/3183
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author Sergei V. German
Anatolii A. Abalymov
Maxim A. Kurochkin
Yuliya Kan
Dmitry A. Gorin
Marina V. Novoselova
author_facet Sergei V. German
Anatolii A. Abalymov
Maxim A. Kurochkin
Yuliya Kan
Dmitry A. Gorin
Marina V. Novoselova
author_sort Sergei V. German
collection DOAJ
description Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Here, we have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological applications, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 μm bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip. The capsule penetration was examined by scanning with fluorescence microscopy followed by quantitative image analysis. The results show that capsules with a size of 0.3 μm passed more easily to the tumor spheroid and penetrated inside. We hope that the device will represent a reliable alternative to in vivo early secondary tumor models and decrease the amount of in vivo experiments in the frame of preclinical study.
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spelling doaj.art-b98879380921445eae602c968383ff4c2023-11-16T20:56:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244318310.3390/ijms24043183Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-CellsSergei V. German0Anatolii A. Abalymov1Maxim A. Kurochkin2Yuliya Kan3Dmitry A. Gorin4Marina V. Novoselova5Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, RussiaTowards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Here, we have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological applications, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 μm bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip. The capsule penetration was examined by scanning with fluorescence microscopy followed by quantitative image analysis. The results show that capsules with a size of 0.3 μm passed more easily to the tumor spheroid and penetrated inside. We hope that the device will represent a reliable alternative to in vivo early secondary tumor models and decrease the amount of in vivo experiments in the frame of preclinical study.https://www.mdpi.com/1422-0067/24/4/3183organ-on-chipcell spheroidmicrofluidiclymph node
spellingShingle Sergei V. German
Anatolii A. Abalymov
Maxim A. Kurochkin
Yuliya Kan
Dmitry A. Gorin
Marina V. Novoselova
Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells
International Journal of Molecular Sciences
organ-on-chip
cell spheroid
microfluidic
lymph node
title Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells
title_full Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells
title_fullStr Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells
title_full_unstemmed Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells
title_short Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells
title_sort plug and play lymph node on chip secondary tumor modeling by the combination of cell spheroid collagen sponge and t cells
topic organ-on-chip
cell spheroid
microfluidic
lymph node
url https://www.mdpi.com/1422-0067/24/4/3183
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