球体
间质细胞
体内
体外
癌症研究
肿瘤微环境
病理
肿瘤细胞
化学
生物医学工程
生物
细胞生物学
医学
生物化学
生物技术
作者
Zhengpeng Wan,Marie Floryan,Mark F. Coughlin,Shun Zhang,Amy X. Zhong,Sarah E. Shelton,Xun Wang,Chong‐Yu Xu,David A. Barbie,Roger D. Kamm
标识
DOI:10.1002/adhm.202201784
摘要
Abstract Previous studies have developed vascularized tumor spheroid models to demonstrate the impact of intravascular flow on tumor progression and treatment. However, these models have not been widely adopted so the vascularization of tumor spheroids in vitro is generally lower than vascularized tumor tissues in vivo. To improve the tumor vascularization level, a new strategy is introduced to form tumor spheroids by adding fibroblasts (FBs) sequentially to a pre‐formed tumor spheroid and demonstrate this method with tumor cell lines from kidney, lung, and ovary cancer. Tumor spheroids made with the new strategy have higher FB densities on the periphery of the tumor spheroid, which tend to enhance vascularization. The vessels close to the tumor spheroid made with this new strategy are more perfusable than the ones made with other methods. Finally, chimeric antigen receptor (CAR) T cells are perfused under continuous flow into vascularized tumor spheroids to demonstrate immunotherapy evaluation using vascularized tumor‐on‐a‐chip model. This new strategy for establishing tumor spheroids leads to increased vascularization in vitro, allowing for the examination of immune, endothelial, stromal, and tumor cell responses under static or flow conditions.
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