Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro

Dafne Barozzi; Fiorella Scagnoli; Federica Barbaglio; Daniela Belloni; Davide Ribezzi; Silvia Farè; Valeria Berno; Riccardo Pinos; Marta Sampietro; Margherita Pauri; Barbara Vergani; Francesco Mantegazza; Paolo Ghia; Cristina Scielzo

doi:10.1016/j.crmeth.2025.101105

Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro

Dafne Barozzi, Fiorella Scagnoli, Federica Barbaglio, Daniela Belloni, Davide Ribezzi, Silvia Farè, Valeria Berno, Riccardo Pinos, Marta Sampietro, Margherita Pauri, Barbara Vergani, Francesco Mantegazza, Paolo Ghia, Cristina Scielzo^*

^*Corresponding author for this work

Regenerative Medicine and Stem Cells

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

This work focused on generating a three-dimensional (3D) in vitro dynamic model to study chronic lymphocytic leukemia (CLL) cell dissemination, homing, and mechanisms of therapy resistance. We used a gelatin-based, hard porous biomaterial as a support matrix to develop 3D tissue-like models of the human lymph node and bone marrow, which were matured inside bioreactors under dynamic perfusion of medium. Comparing static and dynamic cultures of these 3D constructs revealed that perfusion promoted a tissue-like internal organization of cells, characterized by the expression of specific functional markers and deposition of an intricate extracellular matrix protein network. Recirculation of CLL cells within the dynamic system led to changes in leukemic cell behavior and in the expression of key markers involved in tumor progression. These findings suggest that the model is well suited for investigating the pathophysiological mechanisms of CLL and potentially other hematological malignancies.

Original language	English
Article number	101105
Number of pages	29
Journal	Cell reports methods
Volume	5
Issue number	7
Early online date	11 Jul 2025
DOIs	https://doi.org/10.1016/j.crmeth.2025.101105
Publication status	Published - 21 Jul 2025

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Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitroFinal published version, 61.6 MBLicence: CC BY

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Barozzi, D., Scagnoli, F., Barbaglio, F., Belloni, D., Ribezzi, D., Farè, S., Berno, V., Pinos, R., Sampietro, M., Pauri, M., Vergani, B., Mantegazza, F., Ghia, P., & Scielzo, C. (2025). Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro. Cell reports methods, 5(7), Article 101105. https://doi.org/10.1016/j.crmeth.2025.101105

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title = "Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro",

abstract = "This work focused on generating a three-dimensional (3D) in vitro dynamic model to study chronic lymphocytic leukemia (CLL) cell dissemination, homing, and mechanisms of therapy resistance. We used a gelatin-based, hard porous biomaterial as a support matrix to develop 3D tissue-like models of the human lymph node and bone marrow, which were matured inside bioreactors under dynamic perfusion of medium. Comparing static and dynamic cultures of these 3D constructs revealed that perfusion promoted a tissue-like internal organization of cells, characterized by the expression of specific functional markers and deposition of an intricate extracellular matrix protein network. Recirculation of CLL cells within the dynamic system led to changes in leukemic cell behavior and in the expression of key markers involved in tumor progression. These findings suggest that the model is well suited for investigating the pathophysiological mechanisms of CLL and potentially other hematological malignancies.",

author = "Dafne Barozzi and Fiorella Scagnoli and Federica Barbaglio and Daniela Belloni and Davide Ribezzi and Silvia Far{\`e} and Valeria Berno and Riccardo Pinos and Marta Sampietro and Margherita Pauri and Barbara Vergani and Francesco Mantegazza and Paolo Ghia and Cristina Scielzo",

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doi = "10.1016/j.crmeth.2025.101105",

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Barozzi, D, Scagnoli, F, Barbaglio, F, Belloni, D, Ribezzi, D, Farè, S, Berno, V, Pinos, R, Sampietro, M, Pauri, M, Vergani, B, Mantegazza, F, Ghia, P & Scielzo, C 2025, 'Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro', Cell reports methods, vol. 5, no. 7, 101105. https://doi.org/10.1016/j.crmeth.2025.101105

TY - JOUR

T1 - Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro

AU - Barozzi, Dafne

AU - Scagnoli, Fiorella

AU - Barbaglio, Federica

AU - Belloni, Daniela

AU - Ribezzi, Davide

AU - Farè, Silvia

AU - Berno, Valeria

AU - Pinos, Riccardo

AU - Sampietro, Marta

AU - Pauri, Margherita

AU - Vergani, Barbara

AU - Mantegazza, Francesco

AU - Ghia, Paolo

AU - Scielzo, Cristina

PY - 2025/7/21

Y1 - 2025/7/21

N2 - This work focused on generating a three-dimensional (3D) in vitro dynamic model to study chronic lymphocytic leukemia (CLL) cell dissemination, homing, and mechanisms of therapy resistance. We used a gelatin-based, hard porous biomaterial as a support matrix to develop 3D tissue-like models of the human lymph node and bone marrow, which were matured inside bioreactors under dynamic perfusion of medium. Comparing static and dynamic cultures of these 3D constructs revealed that perfusion promoted a tissue-like internal organization of cells, characterized by the expression of specific functional markers and deposition of an intricate extracellular matrix protein network. Recirculation of CLL cells within the dynamic system led to changes in leukemic cell behavior and in the expression of key markers involved in tumor progression. These findings suggest that the model is well suited for investigating the pathophysiological mechanisms of CLL and potentially other hematological malignancies.

AB - This work focused on generating a three-dimensional (3D) in vitro dynamic model to study chronic lymphocytic leukemia (CLL) cell dissemination, homing, and mechanisms of therapy resistance. We used a gelatin-based, hard porous biomaterial as a support matrix to develop 3D tissue-like models of the human lymph node and bone marrow, which were matured inside bioreactors under dynamic perfusion of medium. Comparing static and dynamic cultures of these 3D constructs revealed that perfusion promoted a tissue-like internal organization of cells, characterized by the expression of specific functional markers and deposition of an intricate extracellular matrix protein network. Recirculation of CLL cells within the dynamic system led to changes in leukemic cell behavior and in the expression of key markers involved in tumor progression. These findings suggest that the model is well suited for investigating the pathophysiological mechanisms of CLL and potentially other hematological malignancies.

U2 - 10.1016/j.crmeth.2025.101105

DO - 10.1016/j.crmeth.2025.101105

M3 - Article

C2 - 40651477

SN - 2667-2375

VL - 5

JO - Cell reports methods

JF - Cell reports methods

IS - 7

M1 - 101105

ER -

Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro

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