Polyvinyl alcohol scaffolds and supplementation support 3D and sphere culturing of human cancer cell lines by reducing apoptosis and promoting cellular proliferation

Polyvinyl alcohol scaffolds and supplementation support 3D and sphere culturing of human cancer cell lines by reducing apoptosis and promoting cellular proliferation
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聚乙烯醇支架和补充剂通过减少细胞凋亡和促进细胞增殖支持人类癌细胞系的 3D 和球形培养

DOI:
10.1111/gtc.12843
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发表时间:
2021
期刊:
影响因子:
2.1
通讯作者:
Kato Mitsuyasu
Kato Mitsuyasu
中科院分区:
生物学4区
文献类型:
--
作者:
Okita Yukari;Zheng Ling;Kawanishi Kunio;Miyoshi Hirotoshi;Yanagihara Kazuyoshi;Kato Mitsuyasu

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三维(3D)培养模拟体内肿瘤微环境的异质细胞条件,与2D单层培养细胞相比,已建立的癌细胞系(球体培养)或患者来源的癌细胞(有机培养)的3D培养经常用于癌症研究或药物筛选和评估。为了建立更经济、更省时的癌细胞三维培养方法,我们在球形培养液中添加了聚乙烯醇(PVA),发现乳腺癌细胞和胰腺癌细胞的3D球形培养显著增加。从机理上讲,我们发现PVA可以防止细胞死亡,促进细胞增殖,同时保持与茎干相关的基因表达水平。此外,我们还展示了由交联型PVA制成的聚乙烯醇缩甲醛(PVF)3D支架可以在无血清的长期3D培养中发挥作用,以支持不同类型癌细胞的球形或肿瘤样细胞团的维持。综上所述,我们证明了PVA和PVF在人类癌细胞系培养方案中的有效性。
Three‐dimensional (3D) culturing mimics the heterogeneous cellular conditions of the in vivo tumor microenvironment compared to 2D monolayer‐cultured cells and 3D cultures of established cancer cell lines (sphere culture) or patient‐derived cancer cells (organoid culture) are frequently used for cancer research or drug screening and evaluation. To establish more cost and time‐efficient 3D culture methods for cancer cell lines, we supplemented sphere culture medium with polyvinyl alcohol (PVA) and found that 3D sphere cultures of breast and pancreatic cancer cell lines were significantly increased. Mechanistically, we found that PVA prevented cell death and promoted cellular proliferation while maintaining levels of stemness‐related gene expression. Furthermore, we showed that polyvinyl formal resin (PVF) 3D scaffolds made by cross‐linked PVA can function in serum‐free, long‐term 3D cultures to support maintenance of sphere‐ or tumor‐like cell masses for diverse cancer cell types. Taken together, we demonstrate the effectiveness of PVA and PVF in human cancer cell line culture protocols.
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