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

IF 4.5 Q1 BIOCHEMICAL RESEARCH METHODS

Cell Reports Methods Pub Date : 2025-07-21 Epub Date: 2025-07-11 DOI:10.1016/j.crmeth.2025.101105

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

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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.

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动态刺激促进体外三维人淋巴微环境模型的功能组织样组织。

本研究的重点是建立一个三维（3D）体外动态模型，研究慢性淋巴细胞白血病（CLL）细胞的播散、归巢和耐药机制。我们使用一种基于明胶的硬多孔生物材料作为支撑基质，在生物反应器中动态灌注培养基下成熟人体淋巴结和骨髓的三维组织样模型。比较这些三维结构的静态和动态培养表明，灌注促进了细胞的组织样内部组织，其特征是特定功能标记的表达和复杂的细胞外基质蛋白网络的沉积。CLL细胞在动态系统内的再循环导致白血病细胞行为和参与肿瘤进展的关键标志物表达的变化。这些发现表明，该模型非常适合于研究CLL和其他潜在的血液系统恶性肿瘤的病理生理机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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