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In vitro experimental models and their molding technology of tumor cell

Wang Gao Wang Xiao-Chen Liu Ting Liu Ru-Chuan Liu Li-Yu

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In vitro experimental models and their molding technology of tumor cell

Wang Gao, Wang Xiao-Chen, Liu Ting, Liu Ru-Chuan, Liu Li-Yu
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  • 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.
      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).
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    Irimia D, Toner M 2009 Integr. Biol. 1 506

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    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

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    Derby B 2012 Science 338 921

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    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

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

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

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    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

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    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

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Publishing process
  • Received Date:  08 August 2016
  • Accepted Date:  24 August 2016
  • Published Online:  05 September 2016

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