搜索

x

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

癌细胞体外实验模型及成型技术现状和展望

王高 王晓晨 刘婷 刘如川 刘雳宇

引用本文:
Citation:

癌细胞体外实验模型及成型技术现状和展望

王高, 王晓晨, 刘婷, 刘如川, 刘雳宇

In vitro experimental models and their molding technology of tumor cell

Wang Gao, Wang Xiao-Chen, Liu Ting, Liu Ru-Chuan, Liu Li-Yu
PDF
导出引用
  • 传统的癌症研究是通过观察实验小白鼠的活体组织切片了解肿瘤的形成及癌症的各阶段发展情况,相比于活体实验,癌细胞的体外实验因为可以灵活地操控实验变量和实时观测癌细胞生长和发育的特点从而得以快速发展. 但进一步的研究发现,在诸如培养皿二维环境中培养的细胞的行为在很大程度上与其实际所处的三维环境中的细胞行为有着巨大的差异. 因此借助于微加工和微流体技术以及近年来蓬勃发展的生物3D打印技术、飞秒激光直写技术和水凝胶的紫外光固化等技术,越来越多的癌细胞体外三维实验模型得以制造并用于癌症的研究. 但同时,现有的技术也面临着精度与速度的矛盾和模型材料的生物相容性等问题. 本文讨论了二维及三维癌细胞体外侵袭转移实验的模型及制造技术的优缺点,简要介绍了最新的研究进展,分析提出了未来几年三维实验模型成型技术的发展方向,为相关研究提供新的实验思路.
    Traditional cancer researches focus on the analyses of the mice biopsy in order to understand the formation of cancer and the stage of cancer development. In contrast to in vivo experiments, in vitro investigation of cancer cells provides the flexible manipulation of the experimental parameters and the real time observation of the growth and reproduction of cancer cells, thus has been developing rapidly. However, further studies have demonstrated that cells' behavior in a two-dimensional (2D) environment, e.g. Petri dish, is dramatically different from that in a three-dimensional (3D) environment. Therefore, with assistance of bio-microfluidic chips, 3D bio-printing, direct femtosecond laser writing technology and UV curing hydrogel technology, an increasing number of 3D models have been developed to investigate the behaviors of cancer cells in vitro. Nevertheless, the existing technology is also facing the contradiction between accuracy and speed requirements, as well as the biocompatibility and biodegradability of scaffold materials in use. In this paper, we first summarize and compare present 2D models, e. g. Agar Plate and Boyden Assay, and the developing 3D models in vitro experimental approaches as mentioned above, and discuss the merits of these fabricating technologies. Then we focus on the recent progress and achievements of 3D bio-techniques, especially the successful applications in probing the invasion behaviors of cancer cells. Though significant progress has been made from 2D to 3D approaches and these in vitro experimental models are becoming more flawless in simulating the in vivo environment of cells, the following challenges remain: 1) biocompatible material with the appropriate mechanic properties simulating the environment in vivo; 2) the viability of cells in the complex 3D model with of biomaterial, especially during the laser or UV-assisted gelation of hydrogels; 3) the speed and resolution of the present 3D fabrication technologies; 4) the in situ observation and control of cells. Nevertheless, with the development of 3D bio-technologies, breakthroughs can be expected in solving those problems, and thus will guide the 3D experimental models for the invasion of cancer cells in next few years. This will eventually help people in the war towards cancers, and at the same time provide new experimental approaches for other relevant researches in the interdisciplinary fields of biology, physics, chemistry, materials and engineering.
      通信作者: 刘如川, phyliurc@cqu.edu.cn;liu@iphy.ac.cn ; 刘雳宇, phyliurc@cqu.edu.cn;liu@iphy.ac.cn
    • 基金项目: 国家重点基础研究发展计划(批准号:2013CB837200)、国家自然科学基金(批准号:11474345)和重庆市前沿与应用基础研究计划(批准号:cstc2013jcyjA10047)资助的课题.
      Corresponding author: Liu Ru-Chuan, phyliurc@cqu.edu.cn;liu@iphy.ac.cn ; Liu Li-Yu, phyliurc@cqu.edu.cn;liu@iphy.ac.cn
    • Funds: Project supported by the National Basic Research Program of China (Grant No. 2013CB837200), the National Natural Science Foundation of China (Grant No. 11474345), and the Fundamental and Advanced Research Program of Chongqing, China (Grant No. cstc2013jcyjA10047).
    [1]

    Sleeman J, Steeg P S 2010 Eur. J. Cancer 46 1177

    [2]

    Steeg P S, Theodorescu D 2008 Nat. Clin. Pract. Onco. 5 206

    [3]

    Hanahan D, Weinberg R A 2011 Cell 144 646

    [4]

    Frisch S M, Ruoslahti E 1997 Curr. Opin. Cell Biol. 9 701

    [5]

    Xu W, Mezencev R, Kim B, Wang L, McDonald J, Sulchek T 2012 PLoS One 7 e46609

    [6]

    Discher D E, Janmey P, Wang Y L 2005 Science 310 1139

    [7]

    Liu W F, Nelson C M, Pirone D M, Chen C S 2006 J. Cell Biol. 173 431

    [8]

    Pishvaian M J, Feltes C M, Thompson P, Bussemakers M J, Schalken J A, Byers S W 1999 Cancer Res. 59 947

    [9]

    Nieman M T, Prudoff R S, Johnson K R, Wheelock M J 1999 J. Cell Biol. 147 631

    [10]

    Poincloux R, Collin O, Lizarraga F, Romao M, Debray M, Piel M, Chavrier P 2011 Proc. Natl. Acad. Sci. USA 108 1943

    [11]

    Chabottaux V, Noel A 2007 Clin. Exp. Metastasis 24 647

    [12]

    Hegedus L, Cho H, Xie X, Eliceiri G L 2008 J. Cell Physiol. 216 480

    [13]

    Pampaloni F, Reynaud E G, Stelzer E H 2007 Nat. Rev. Mol. Cell Biol. 8 839

    [14]

    Meyer A S, Hughes-Alford S K, Kay J E, Castillo A, Wells A, Gertler F B, Lauffenburger D A 2012 J. Cell Biol. 197 721

    [15]

    Sung K E, Su X, Berthier E, Pehlke C, Friedl A, Beebe D J 2013 PLoS One 8 e76373

    [16]

    Trepat X, Wasserman M R, Angelini T E, Millet E, Weitz D A, Butler J P, Fredberg J J 2009 Nat. Phys. 5 426

    [17]

    Irimia D, Toner M 2009 Integr. Biol. 1 506

    [18]

    Wu P H, Giri A, Sun S X, Wirtz D 2014 Proc. Natl. Acad. Sci. USA 111 3949

    [19]

    Malda J, Visser J, Melchels F P, Jungst T, Hennink W E, Dhert W J A, Groll J, Hutmacher D W 2013 Adv. Mater. 25 5011

    [20]

    Derby B 2012 Science 338 921

    [21]

    Zorlutuna P, Annabi N, Camci-Unal G, Nikkhah M, Cha J M, Nichol J W, Manbachi A, Bae H, Chen S, Khademhosseini A 2012 Adv. Mater. 24 1782

    [22]

    Xu T, Zhao W, Zhu J M, Albanna M Z, Yoo J J, Atala A 2013 Biomaterials 34 130

    [23]

    Ahn S, Lee H, Lee E J, Kim G H 2014 J. Mater. Chem. B 2 2773

    [24]

    Kang H W, Lee S J, Ko I K, Kengla C, James J, Yoo J, Atala A 2016 Nat. Biotechnol. 34 312

    [25]

    Gill A A, Ortega I, Kelly S, Claeyssens F 2015 Biomed. Microdevices 17 27

    [26]

    Selimis A, Mironov V, Farsari M 2015 Microelectron. Eng. 132 83

    [27]

    Wang J, Auyeung R C, Kim H, Kim H, Charipar N A, Pique A 2010 Adv. Mater. 22 4462

    [28]

    Buckmann T, Stenger N, Kadic M, Kaschke J, Frolich A, Kennerknecht T, Eberl C, Thiel M, Wegener M 2012 Adv. Mater. 24 2710

    [29]

    Kim S, Qiu F, Kim S, Ghanbari A, Moon C, Zhang L, Nelson B J, Choi H 2013 Adv. Mater. 25 5863

    [30]

    Cha C, Soman P, Zhu W, Nikkhah M, Camci-Unal G, Chen S, Khademhosseini A 2014 Biomater. Sci. 2 703

    [31]

    Hong S, Sycks D, Chan H F, Lin S, Lopez G P, Guilak F, Leong K M, Zhao X 2015 Adv. Mater. 27 4035

    [32]

    Soman P, Kelber J A, Lee J W, Wright T N, Vecchio K S, Klemke R L, Chen S 2012 Biomaterials 33 7064

    [33]

    Soman P, Fozdar D Y, Lee J W, Phadke A, Varghese S, Chen S 2012 Soft Matter 8 4946

    [34]

    Liu L, Sun B, Pedersen J N, Yong K A, Getzenberg R H, Stone H A, Austin R H 2011 Proc. Natl. Acad. Sci. USA 108 6853

    [35]

    Han W, Chen S, Yuan W, Fan Q, Tian J, Wang X, Chen L, Zhang X, Wei W, Liu R, Qu J, Jiao Y, Austin R H, Liu L 2016 Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1610347113

    [36]

    A. Sydney Gladman, Matsumoto E A, Nuzzo R G, Mahadevan L, Lewis J A 2016 Nature. Mater. 15 413

  • [1]

    Sleeman J, Steeg P S 2010 Eur. J. Cancer 46 1177

    [2]

    Steeg P S, Theodorescu D 2008 Nat. Clin. Pract. Onco. 5 206

    [3]

    Hanahan D, Weinberg R A 2011 Cell 144 646

    [4]

    Frisch S M, Ruoslahti E 1997 Curr. Opin. Cell Biol. 9 701

    [5]

    Xu W, Mezencev R, Kim B, Wang L, McDonald J, Sulchek T 2012 PLoS One 7 e46609

    [6]

    Discher D E, Janmey P, Wang Y L 2005 Science 310 1139

    [7]

    Liu W F, Nelson C M, Pirone D M, Chen C S 2006 J. Cell Biol. 173 431

    [8]

    Pishvaian M J, Feltes C M, Thompson P, Bussemakers M J, Schalken J A, Byers S W 1999 Cancer Res. 59 947

    [9]

    Nieman M T, Prudoff R S, Johnson K R, Wheelock M J 1999 J. Cell Biol. 147 631

    [10]

    Poincloux R, Collin O, Lizarraga F, Romao M, Debray M, Piel M, Chavrier P 2011 Proc. Natl. Acad. Sci. USA 108 1943

    [11]

    Chabottaux V, Noel A 2007 Clin. Exp. Metastasis 24 647

    [12]

    Hegedus L, Cho H, Xie X, Eliceiri G L 2008 J. Cell Physiol. 216 480

    [13]

    Pampaloni F, Reynaud E G, Stelzer E H 2007 Nat. Rev. Mol. Cell Biol. 8 839

    [14]

    Meyer A S, Hughes-Alford S K, Kay J E, Castillo A, Wells A, Gertler F B, Lauffenburger D A 2012 J. Cell Biol. 197 721

    [15]

    Sung K E, Su X, Berthier E, Pehlke C, Friedl A, Beebe D J 2013 PLoS One 8 e76373

    [16]

    Trepat X, Wasserman M R, Angelini T E, Millet E, Weitz D A, Butler J P, Fredberg J J 2009 Nat. Phys. 5 426

    [17]

    Irimia D, Toner M 2009 Integr. Biol. 1 506

    [18]

    Wu P H, Giri A, Sun S X, Wirtz D 2014 Proc. Natl. Acad. Sci. USA 111 3949

    [19]

    Malda J, Visser J, Melchels F P, Jungst T, Hennink W E, Dhert W J A, Groll J, Hutmacher D W 2013 Adv. Mater. 25 5011

    [20]

    Derby B 2012 Science 338 921

    [21]

    Zorlutuna P, Annabi N, Camci-Unal G, Nikkhah M, Cha J M, Nichol J W, Manbachi A, Bae H, Chen S, Khademhosseini A 2012 Adv. Mater. 24 1782

    [22]

    Xu T, Zhao W, Zhu J M, Albanna M Z, Yoo J J, Atala A 2013 Biomaterials 34 130

    [23]

    Ahn S, Lee H, Lee E J, Kim G H 2014 J. Mater. Chem. B 2 2773

    [24]

    Kang H W, Lee S J, Ko I K, Kengla C, James J, Yoo J, Atala A 2016 Nat. Biotechnol. 34 312

    [25]

    Gill A A, Ortega I, Kelly S, Claeyssens F 2015 Biomed. Microdevices 17 27

    [26]

    Selimis A, Mironov V, Farsari M 2015 Microelectron. Eng. 132 83

    [27]

    Wang J, Auyeung R C, Kim H, Kim H, Charipar N A, Pique A 2010 Adv. Mater. 22 4462

    [28]

    Buckmann T, Stenger N, Kadic M, Kaschke J, Frolich A, Kennerknecht T, Eberl C, Thiel M, Wegener M 2012 Adv. Mater. 24 2710

    [29]

    Kim S, Qiu F, Kim S, Ghanbari A, Moon C, Zhang L, Nelson B J, Choi H 2013 Adv. Mater. 25 5863

    [30]

    Cha C, Soman P, Zhu W, Nikkhah M, Camci-Unal G, Chen S, Khademhosseini A 2014 Biomater. Sci. 2 703

    [31]

    Hong S, Sycks D, Chan H F, Lin S, Lopez G P, Guilak F, Leong K M, Zhao X 2015 Adv. Mater. 27 4035

    [32]

    Soman P, Kelber J A, Lee J W, Wright T N, Vecchio K S, Klemke R L, Chen S 2012 Biomaterials 33 7064

    [33]

    Soman P, Fozdar D Y, Lee J W, Phadke A, Varghese S, Chen S 2012 Soft Matter 8 4946

    [34]

    Liu L, Sun B, Pedersen J N, Yong K A, Getzenberg R H, Stone H A, Austin R H 2011 Proc. Natl. Acad. Sci. USA 108 6853

    [35]

    Han W, Chen S, Yuan W, Fan Q, Tian J, Wang X, Chen L, Zhang X, Wei W, Liu R, Qu J, Jiao Y, Austin R H, Liu L 2016 Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1610347113

    [36]

    A. Sydney Gladman, Matsumoto E A, Nuzzo R G, Mahadevan L, Lewis J A 2016 Nature. Mater. 15 413

  • [1] 朱海龙, 李雪迎, 童洪辉. 三维数值模拟射频热等离子体的物理场分布. 物理学报, 2021, 70(15): 155202. doi: 10.7498/aps.70.20202135
    [2] 李双双, 赵全堂, 曹树春, 冉朝晖, 申晓康, 赵书俊, 张子民. 高能电子三维成像技术实验研究. 物理学报, 2021, 70(18): 184204. doi: 10.7498/aps.70.20210686
    [3] 胡嘉懿, 张文欢, 柴振华, 施保昌, 汪一航. 三维不可压缩流的12速多松弛格子Boltzmann模型. 物理学报, 2019, 68(23): 234701. doi: 10.7498/aps.68.20190984
    [4] 麻礼东, 杨光辉, 张晟, 林平, 田园, 杨磊. 三维漏斗中颗粒物质堵塞问题的数值实验研究. 物理学报, 2018, 67(4): 044501. doi: 10.7498/aps.67.20171813
    [5] 潘安, 张晓菲, 王彬, 赵青, 史祎诗. 厚样品三维叠层衍射成像的实验研究. 物理学报, 2016, 65(1): 014204. doi: 10.7498/aps.65.014204
    [6] 王华光, 张泽新. 摄像显微技术在实验软物质物理中的应用. 物理学报, 2016, 65(17): 178705. doi: 10.7498/aps.65.178705
    [7] 司铁岩, 袁军华, 吴艺林, 唐建新. 细菌运动中的物理生物学. 物理学报, 2016, 65(17): 178703. doi: 10.7498/aps.65.178703
    [8] 张宇, 唐志列, 吴泳波, 束刚. 基于声透镜的三维光声成像技术. 物理学报, 2015, 64(24): 240701. doi: 10.7498/aps.64.240701
    [9] 鲁金蕾, 王晓晨, 容晓晖, 刘雳宇. 三维微纳米制造技术在癌症生物物理研究中的应用. 物理学报, 2015, 64(5): 058705. doi: 10.7498/aps.64.058705
    [10] 徐莹莹, 阚玉和, 武洁, 陶委, 苏忠民. 并苯纳米环[6]CA及其衍生物的电子结构和光物理性质的密度泛函理论研究. 物理学报, 2013, 62(8): 083101. doi: 10.7498/aps.62.083101
    [11] 刘冬, 严建华, 王飞, 黄群星, 池涌, 岑可法. 火焰烟黑三维温度场和浓度场同时重建实验研究. 物理学报, 2011, 60(6): 060701. doi: 10.7498/aps.60.060701
    [12] 龚伯仪, 周欣, 赵晓鹏. 光频三维各向同性左手超材料结构单元模型的仿真设计. 物理学报, 2011, 60(4): 044101. doi: 10.7498/aps.60.044101
    [13] 韩奎, 李明雪, 李海鹏, 吴玉喜, 唐刚, 吴琼华, 童星, 钟琪. 二维电荷转移结构轮烯衍生物光学性质理论研究. 物理学报, 2010, 59(9): 6250-6255. doi: 10.7498/aps.59.6250
    [14] 莫嘉琪, 林万涛. 三维赤道海气振子模型的近似解. 物理学报, 2008, 57(3): 1291-1294. doi: 10.7498/aps.57.1291
    [15] 刘 凌, 苏燕辰, 刘崇新. 新三维混沌系统及其电路仿真实验. 物理学报, 2007, 56(4): 1966-1970. doi: 10.7498/aps.56.1966
    [16] 董慧媛, 刘 楣, 吴宗汉, 汪 静, 王振林. 由介质球构成的三维光子晶体能带结构的平面波研究. 物理学报, 2005, 54(7): 3194-3199. doi: 10.7498/aps.54.3194
    [17] 邵元智, 蓝图, 林光明. 三维动态Ising模型中的非平衡相变:三临界点的存在. 物理学报, 2001, 50(5): 942-947. doi: 10.7498/aps.50.942
    [18] 季达人, 张剑波, 应和平. 三维随机点阵三态矢量Potts模型Monte Carlo模拟. 物理学报, 1992, 41(7): 1162-1166. doi: 10.7498/aps.41.1162
    [19] 滕保华. 三维Ising模型的Green函数方法处理. 物理学报, 1991, 40(5): 826-832. doi: 10.7498/aps.40.826
    [20] 石赫, 许以超, 郝柏林. 三维晶格统计模型的一种封闭的近似解. 物理学报, 1978, 27(1): 47-62. doi: 10.7498/aps.27.47
计量
  • 文章访问数:  5349
  • PDF下载量:  330
  • 被引次数: 0
出版历程
  • 收稿日期:  2016-08-08
  • 修回日期:  2016-08-24
  • 刊出日期:  2016-09-05

/

返回文章
返回