仿生肿瘤微环境模型弥合了体外和体内系统之间的差距，并作为解决如何重建与真实组织相关的细胞和系统复杂性的建模挑战的有效方法。我们的实验室开发了一种离体大鼠肠系膜培养模型，可以在完整的组织环境中同时研究血液和淋巴微血管网络的重塑。鉴于血管生成和淋巴管生成是癌症进展的关键因素，本研究的目的是将组织和肿瘤球体培养方法结合起来，建立一种新型的离体肿瘤球体组织模型，验证其在评估癌细胞效应方面的用途。局部微血管环境的行为。通过悬滴培养形成 H1299 或 A549 肿瘤球体，并将其接种到从成年雄性 Wistar 大鼠收获的大鼠肠系膜组织上。移植球体的组织在无血清培养基中培养 3 至 5 天。 PECAM、NG2、CD11b 和 αSMA 标记分别识别内皮细胞、周细胞、免疫细胞和平滑肌细胞。延时成像证实了癌细胞类型特异性迁移。除了增加表明淋巴管生成的 PECAM 阳性毛细血管萌芽和 LYVE-1 阳性内皮细胞延伸外，肿瘤球体的存在还诱导淋巴管/血管连接的形成以及以不连续 LYVE-1 标记为特征的混合、镶嵌血管的形成。结果支持应用新型肿​​瘤球体微环境模型来研究癌细胞-微血管相互作用。© 2024。作者获得生物医学工程学会独家许可。

Biomimetic tumor microenvironment models bridge the gap between in vitro and in vivo systems and serve as a useful way to address the modeling challenge of how to recreate the cell and system complexity associated with real tissues. Our laboratory has developed an ex vivo rat mesentery culture model, which allows for simultaneous investigation of blood and lymphatic microvascular network remodeling in an intact tissue environment. Given that angiogenesis and lymphangiogenesis are key contributors to the progression of cancer, the objective of this study was to combine tissue and tumor spheroid culture methods to establish a novel ex vivo tumor spheroid-tissue model by verifying its use for evaluating the effects of cancer cell behavior on the local microvascular environment. H1299 or A549 tumor spheroids were formed via hanging drop culture and seeded onto rat mesenteric tissues harvested from adult male Wistar rats. Tissues with transplanted spheroids were cultured in serum-free media for 3 to 5 days. PECAM, NG2, CD11b, and αSMA labeling identified endothelial cells, pericytes, immune cells, and smooth muscle cells, respectively. Time-lapse imaging confirmed cancer cell type specific migration. In addition to increasing PECAM positive capillary sprouting and LYVE-1 positive endothelial cell extensions indicative of lymphangiogenesis, tumor spheroid presence induced the formation of lymphatic/blood vessel connections and the formation of hybrid, mosaic vessels that were characterized by discontinuous LYVE-1 labeling. The results support the application of a novel tumor spheroid microenvironment model for investigating cancer cell-microvascular interactions.© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.