Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. Until now, in vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B lymphomas remain scarce while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on the encapsulation of cells inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating extracellular matrix and/or stromal cells. Lymphoma B cells and stromal cells dynamically formed self-organized 3D spheroids, thus initiating a coevolution of these two cell types, reflecting their bidirectional crosstalk, and recapitulating the heterogeneity of B-NHL subtypes. In addition, this approach makes it suitable to assess in a relevant in vitro model the activity of new therapeutic agents in B-NHL.

中文翻译：

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在模拟淋巴瘤肿瘤小生境的新3D模型中，基质细胞调节恶性B细胞的空间组织，存活和药物反应

非霍奇金B细胞淋巴瘤（B-NHL）主要在淋巴结内以肿瘤细胞及其周围微环境的密集堆积聚集形式发展，从而形成了针对每种淋巴瘤亚型的肿瘤位。到目前为止，仍然缺乏模拟生物力学力，细胞微环境和B淋巴瘤的3D组织的体外临床前模型，而所有这些参数均是决定淋巴瘤发生和耐药性的关键因素。使用基于在可渗透，有弹性和中空藻酸盐微球内部封装细胞的微流控方法，我们开发了一种新的可调谐3D模型，其中包含细胞外基质和/或基质细胞。淋巴瘤B细胞和基质细胞动态形成自组织的3D球体，从而启动了这两种细胞类型的协同进化，反映了它们的双向串扰，并概括了B-NHL亚型的异质性。另外，这种方法使其适合在相关的体外模型中评估B-NHL中新治疗剂的活性。