New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay.

New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay.
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微流控检测中促进肿瘤球体血管化的新策略

DOI:
10.1002/adhm.202201784
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发表时间:
2023-06
影响因子:
10
通讯作者:
Kamm, Roger D.
Kamm, Roger D.
中科院分区:
工程技术1区
文献类型:
--
作者:
Wan, Zhengpeng;Floryan, Marie A.;Coughlin, Mark F.;Zhang, Shun;Zhong, Amy X.;Shelton, Sarah E.;Wang, Xun;Xu, Chenguang;Barbie, David A.;Kamm, Roger D.

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先前的研究开发了血管化的肿瘤球体模型,以证明血管内流动对肿瘤进展和治疗的影响。但是,这些模型尚未被广泛采用,因此体外肿瘤球体的血管化通常低于体内的血管化肿瘤组织。为了提高肿瘤血管化水平,引入了一种新的策略来形成肿瘤球体,通过将成纤维细胞(FBS)顺序添加到预先形成的肿瘤球体中,并用来自肾脏,肺和卵巢癌的肿瘤细胞系证明了这种方法。用新策略制成的肿瘤球体在肿瘤球体的周围具有较高的FB密度,这倾向于增强血管形成。用这种新策略制成的肿瘤球体接近的血管比用其他方法制成的血管更加灌注。最后,将嵌合抗原受体(CAR)T细胞灌注在连续流入血管化肿瘤球体下,以使用血管化肿瘤模型来证明免疫疗法评估。建立肿瘤球体的新策略会导致体外血管形成增加,从而检查在静态或流动条件下的免疫,内皮,基质和肿瘤细胞反应。
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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