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On-line Access: 2024-12-30

Received: 2023-09-03

Revision Accepted: 2024-03-04

Crosschecked: 2024-12-30

Cited: 0

Clicked: 1129

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ling YU

https://orcid.org/0000-0002-6726-281X

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.12 P.1097-1107

http://doi.org/10.1631/jzus.B2300617


Co-culture of natural killer cells and tumor spheroids on a heterogeneous multilayer paper stack


Author(s):  Yuanyuan XIE, Xiaoyan YANG, Rong PAN, Lixia GAO, Ling YU

Affiliation(s):  Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, Institute for Clean Energy and Advanced Materials, School of Materials and Energy, Southwest University, Chongqing400715, China; more

Corresponding email(s):   lingyu12@swu.edu.cn

Key Words:  Multilayer paper stack, Co-culture, Tumor spheroid, Human umbilical vein endothelial cell (HUVEC), Natural killer cell (NK cell), Migration


Yuanyuan XIE, Xiaoyan YANG, Rong PAN, Lixia GAO, Ling YU. Co-culture of natural killer cells and tumor spheroids on a heterogeneous multilayer paper stack[J]. Journal of Zhejiang University Science B, 2024, 25(12): 1097-1107.

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author="Yuanyuan XIE, Xiaoyan YANG, Rong PAN, Lixia GAO, Ling YU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="12",
pages="1097-1107",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300617"
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%T Co-culture of natural killer cells and tumor spheroids on a heterogeneous multilayer paper stack
%A Yuanyuan XIE
%A Xiaoyan YANG
%A Rong PAN
%A Lixia GAO
%A Ling YU
%J Journal of Zhejiang University SCIENCE B
%V 25
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%P 1097-1107
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%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300617

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T1 - Co-culture of natural killer cells and tumor spheroids on a heterogeneous multilayer paper stack
A1 - Yuanyuan XIE
A1 - Xiaoyan YANG
A1 - Rong PAN
A1 - Lixia GAO
A1 - Ling YU
J0 - Journal of Zhejiang University Science B
VL - 25
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SP - 1097
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2300617


Abstract: 
Multilayer paper-based cell culture, as an in vitro three-dimensional (3D) cell culture method, has been frequently used to research drug bioavailability, therapeutic efficacy, and dose-limiting toxicity in malignant tumors. This paper proposes a heterogenous multilayer paper stacking co-culture system to establish a model of natural killer (NK) cells moving through the endothelium layer and attacking tumor spheroids. This system consists of three layers: a bottom tumor-spheroid layer, a middle invasion layer, and a top endothelium layer. NK-92 cells were placed in the supernatant on top of the three layers. After two days of co-culture, the attack of tumor spheroids by NK cells was observed. We additionally examined the infiltration of NK-92 cells within the tumor spheroids at different Z-axis depths using a confocal microscope, and the results suggested that the system successfully realizes NK cells traveling cross the endothelium layer to form tumor-infiltrating NK cells (TINKs). The potential application of multilayer paper for co-culture models involving cancer cells and immune cells holds great promise for exploring the interaction dynamics of these two cell types.

自然杀伤细胞与肿瘤球在多层纸基堆叠支架的共培养

谢媛媛1,杨晓艳1,潘茸1,高丽霞2,余玲1
1西南大学材料与能源学院,清洁能源与先进材料研究院,发光分析与分子传感教育部重点实验室,中国重庆市,400715
2重庆文理学院药学院 / 创新靶向药物国际研究院, 创新靶向药物国家地方联合工程研究中心, 中国重庆市, 402160
摘要:多层纸基堆叠支架细胞培养体系作为一种三维(3D)体外细胞培养平台,已被用于评估抗肿瘤药物的疗效。本研究提出了一种基于多层纸基堆叠支架的共培养模型,用于模拟自然杀伤细胞(NK细胞)从内皮层向肿瘤细胞球体迁移并发起攻击的过程。该共培养体系由三层结构组成:底层为肿瘤细胞球体层;中间层为模拟肿瘤间质的侵袭层;顶层为内皮细胞层。NK-92细胞悬浮于培养体系上方的培养基中。经过2天的共培养后,我们观察到NK细胞与肿瘤细胞球体之间发生相互作用。此外,共聚焦显微镜检测结果发现NK-92细胞能够穿过内皮层,在肿瘤细胞球体内部不同深度处浸润,形成肿瘤浸润NK细胞(TINKs),这表明该共培养模型成功模拟了NK细胞向实体肿瘤组织浸润的过程。该多层纸基共培养体系在涉及肿瘤细胞与免疫细胞相互作用的模型研究中具有应用潜力,为探索两种细胞间动力学相互作用提供了条件。

关键词:多层堆叠纸基;共培养;肿瘤球;人脐静脉内皮细胞;人自然杀伤细胞;迁移

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