Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell non-Hodgkin lymphoma, often developing resistance to current treatments. Development and testing of new therapies is hampered by lack of good in vivo and in vitro models mimicking human disease. Here, we developed a lymphoma-...

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Main Authors: Mohammad Jouybar, Aleksandra M. Mikula, Nanouk Zuidmeer, Tanja Konijn, A. Vera de Jonge, Henk P. Roest, Tuna Mutis, Luc J.W. van der Laan, Reina E. Mebius, Jaap M.J. den Toonder, Charlotte M. de Winde
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425001024
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author Mohammad Jouybar
Aleksandra M. Mikula
Nanouk Zuidmeer
Tanja Konijn
A. Vera de Jonge
Henk P. Roest
Tuna Mutis
Luc J.W. van der Laan
Reina E. Mebius
Jaap M.J. den Toonder
Charlotte M. de Winde
author_facet Mohammad Jouybar
Aleksandra M. Mikula
Nanouk Zuidmeer
Tanja Konijn
A. Vera de Jonge
Henk P. Roest
Tuna Mutis
Luc J.W. van der Laan
Reina E. Mebius
Jaap M.J. den Toonder
Charlotte M. de Winde
author_sort Mohammad Jouybar
collection DOAJ
description Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell non-Hodgkin lymphoma, often developing resistance to current treatments. Development and testing of new therapies is hampered by lack of good in vivo and in vitro models mimicking human disease. Here, we developed a lymphoma-on-chip model to investigate the tumor-supportive roles of lymph node stromal cells (LNSCs) – fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) – in the DLBCL microenvironment. The model includes a tubular vessel lined with LECs surrounded by a hydrogel with DLBCL cells and FRCs. Our findings reveal that FRCs promote DLBCL survival and facilitate tumor cell migration towards lymphatic vessels. Moreover, we demonstrate that DLBCL cells increase permeability of lymphatic vessels, which is further enhanced in presence of FRCs. This lymphoma-on-chip model reveals the important role of LNSCs in DLBCL progression, and offers an innovative tool to study the DLBCL microenvironment and test potential therapeutic targets to improve patient outcomes.
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spelling doaj-art-c3e09dfb09774123a5b505ca40b5e8f82025-08-20T02:15:19ZengElsevierMaterials Today Bio2590-00642025-04-013110154410.1016/j.mtbio.2025.101544Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migrationMohammad Jouybar0Aleksandra M. Mikula1Nanouk Zuidmeer2Tanja Konijn3A. Vera de Jonge4Henk P. Roest5Tuna Mutis6Luc J.W. van der Laan7Reina E. Mebius8Jaap M.J. den Toonder9Charlotte M. de Winde10Microsystems, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven, the NetherlandsDepartment of Molecular Cell Biology, Amsterdam UMC Location VU, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the NetherlandsDepartment of Molecular Cell Biology, Amsterdam UMC Location VU, Amsterdam, the NetherlandsDepartment of Molecular Cell Biology, Amsterdam UMC Location VU, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Department of Hematology, Amsterdam UMC Location VU, Amsterdam, the NetherlandsErasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Rotterdam, the NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Department of Hematology, Amsterdam UMC Location VU, Amsterdam, the NetherlandsErasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Rotterdam, the NetherlandsDepartment of Molecular Cell Biology, Amsterdam UMC Location VU, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the NetherlandsMicrosystems, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven, the Netherlands; Corresponding author. Microsystems, Eindhoven University of Technology, Eindhoven, the Netherlands.Department of Molecular Cell Biology, Amsterdam UMC Location VU, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Corresponding author. Department of Molecular Cell Biology, Amsterdam UMC Location VU, Amsterdam, the Netherlands.Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell non-Hodgkin lymphoma, often developing resistance to current treatments. Development and testing of new therapies is hampered by lack of good in vivo and in vitro models mimicking human disease. Here, we developed a lymphoma-on-chip model to investigate the tumor-supportive roles of lymph node stromal cells (LNSCs) – fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) – in the DLBCL microenvironment. The model includes a tubular vessel lined with LECs surrounded by a hydrogel with DLBCL cells and FRCs. Our findings reveal that FRCs promote DLBCL survival and facilitate tumor cell migration towards lymphatic vessels. Moreover, we demonstrate that DLBCL cells increase permeability of lymphatic vessels, which is further enhanced in presence of FRCs. This lymphoma-on-chip model reveals the important role of LNSCs in DLBCL progression, and offers an innovative tool to study the DLBCL microenvironment and test potential therapeutic targets to improve patient outcomes.http://www.sciencedirect.com/science/article/pii/S2590006425001024Lymphoma-on-ChipLymphatic vesselVessel-on-ChipTumor microenvironmentDiffuse large B-Cell lymphomaLymph node
spellingShingle Mohammad Jouybar
Aleksandra M. Mikula
Nanouk Zuidmeer
Tanja Konijn
A. Vera de Jonge
Henk P. Roest
Tuna Mutis
Luc J.W. van der Laan
Reina E. Mebius
Jaap M.J. den Toonder
Charlotte M. de Winde
Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration
Materials Today Bio
Lymphoma-on-Chip
Lymphatic vessel
Vessel-on-Chip
Tumor microenvironment
Diffuse large B-Cell lymphoma
Lymph node
title Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration
title_full Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration
title_fullStr Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration
title_full_unstemmed Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration
title_short Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration
title_sort lymphoma on chip model reveals that lymph node stromal cells promote diffuse large b cell lymphoma survival and migration
topic Lymphoma-on-Chip
Lymphatic vessel
Vessel-on-Chip
Tumor microenvironment
Diffuse large B-Cell lymphoma
Lymph node
url http://www.sciencedirect.com/science/article/pii/S2590006425001024
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