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微流控实验中促进肿瘤球体血管化的新策略

英文原题:New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay.

查看英文原题

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

PubMed 2022/11/15(内容时间) Adv Healthc Mater Q1 · IF 11(JCR 2025)

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中文摘要

以往的研究已开发出血管化肿瘤球模型,用以证明血管内流动对肿瘤进展和治疗的影响。然而,这些模型尚未被广泛采用,因此体外肿瘤球的血管化程度通常低于体内血管化肿瘤组织。为提高肿瘤血管化水平,本文引入一种新策略,即通过将成纤维细胞(FBs)依次加入预先形成的肿瘤球中来形成肿瘤球,并用来自肾癌、肺癌和卵巢癌的肿瘤细胞系对该方法进行了验证。采用新策略制备的肿瘤球在肿瘤球外周具有更高的FB密度,这倾向于增强血管化。与其他方法制备的血管相比,采用该新策略制备的肿瘤球附近的血管具有更好的灌注性。最后,将嵌合抗原受体(CAR)T细胞在连续流动下灌注到血管化肿瘤球中,以展示使用血管化肿瘤芯片模型进行免疫治疗评估。这种建立肿瘤球的新策略可提高体外血管化程度,从而能够在静态或流动条件下检查免疫细胞、内皮细胞、基质细胞和肿瘤细胞的反应。

展开英文摘要原文

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.

论文信息

作者
Wan Z、Floryan MA、Coughlin MF、Zhang S、Zhong AX、Shelton SE、Wang X、Xu C
单位
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.United Kingdom
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Advanced healthcare materials2023 Jun
原文标识
PubMed 36333913 · DOI 10.1002/adhm.202201784