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胶质母细胞瘤干细胞与间充质干细胞融合促进 3D 生物打印模型中的恶性进展。

Fusion between Glioma Stem Cells and Mesenchymal Stem Cells Promotes Malignant Progression in 3D-Bioprinted Models.

机构信息

Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, P. R. China.

School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2022 Aug 10;14(31):35344-35356. doi: 10.1021/acsami.2c06658. Epub 2022 Jul 26.

DOI:10.1021/acsami.2c06658
PMID:35881920
Abstract

The interaction between glioma stem cells (GSCs) and mesenchymal stem cells (MSCs) in the glioma microenvironment is considered to be an important factor in promoting tumor progression, but the mechanism is still not fully elucidated. To further elucidate the interaction between GSCs and MSCs, two 3D-bioprinted tumor models (low-temperature molding and coaxial bioprinting) were used to simulate the tumor growth microenvironment. Cell fusion between GSCs and MSCs was found by the method of Cre-LoxP switch gene and RFP/GFP dual-color fluorescence tracing. The fused cells coexpressed biomarkers of GSCs and MSCs, showing stronger proliferation, cloning, and invasion abilities than GSCs and MSCs. In addition, the fused cells have stronger tumorigenic properties in nude mice, showing the pathological features of malignant tumors. In conclusion, GSCs and MSCs undergo cell fusion in 3D-bioprinted models, and the fused cells have a higher degree of malignancy than parental cells, which promotes the progression of glioma.

摘要

脑胶质瘤干细胞(GSCs)与间质干细胞(MSCs)在脑胶质瘤微环境中的相互作用被认为是促进肿瘤进展的重要因素,但机制仍未完全阐明。为了进一步阐明 GSCs 和 MSCs 之间的相互作用,我们使用两种 3D 生物打印肿瘤模型(低温成型和共轴生物打印)来模拟肿瘤生长微环境。通过 Cre-LoxP 开关基因和 RFP/GFP 双荧光追踪的方法发现 GSCs 和 MSCs 之间发生了细胞融合。融合细胞共表达 GSCs 和 MSCs 的标志物,表现出比 GSCs 和 MSCs 更强的增殖、克隆和侵袭能力。此外,融合细胞在裸鼠中具有更强的致瘤性,表现出恶性肿瘤的病理特征。总之,GSCs 和 MSCs 在 3D 生物打印模型中发生细胞融合,融合细胞的恶性程度比亲本细胞更高,促进了脑胶质瘤的进展。

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