Two-dimensional and three-dimensional cell culture models in vitro: pros and cons
https://doi.org/10.20538/1682-0363-2018-3-188-196
Abstract
Discovery and development of new chemical compounds with putative anti-cancer properties requires reliable predictive preclinical models for in vitro screening of efficacy. Such models mainly include cultures of human cancer cells: two-dimensional (2D) and three-dimensional (3D) cell culture systems. In this review, we discuss the molecular aspects of cells cultured in 2D and 3D, and their relevance to cancer study, focusing on key examples from the recent literature. Advantages, disadvantages and perspectives of described models are also analyzed.
About the Authors
E. S. Galimova
Almazov National Medical Research Center
Russian Federation
Russian Federation
Galimova Elvira S. - PhD, Senior Researcher.
2, Accuratov Str., Saint Petersburg, 197341
M. М. Galagudza
Almazov National Medical Research Center
Russian Federation
Russian Federation
Galagudza Michael M. - DM., Professor, Head of Institute of Experimental Medicine.
2, Accuratov Str., Saint Petersburg, 197341
References
1. Kola I., Landis J. Can the pharmaceutical industry reduce attrition rates? Nature Rev. Drug Dis. 2004; 3 (8): 711–715. DOI: 10.1038/nrd1470.
2. Amelian A., Wasilewska K., Megias D., Winnicka K. Application of standard cell cultures and 3D in vitro tissue models as an effective tool in drug design and development. Pharmacological Reports. 2017; 69 (5): 861–870. DOI: 10.1016/j.pharep.2017.03.014.
3. Santo V.E., Rebelo S.P., Estrada M.F., Alves P.M., Boghaert E., & Brito C. Drug screening in 3D in vitro tumor models: overcoming current pitfalls of efficacy read – outs. Biotechnology journal. 2017; 12 (1). DOI: 10.1002/ biot.201600505.
4. Fong E.L., Harrington D.A., Farach-Carson M.C., Yu.H. Heralding a new paradigm in 3D tumor modeling. Biomaterials. 2016; 108: 197–213. DOI: 10.1016/j.biomaterials.2016.08.052.
5. Duval K., Grover H., Han L.H., Mou Y., Pegoraro A.F., Fredberg J., Chen Z. Modeling Physiological Events in 2D vs. 3D Cell Culture. Physiology. 2017; 32 (4): 266–277. DOI: 10.1152/physiol.00036.2016.
6. Lovitt C.J., Shelper T.B., Avery V.M. Advanced cell culture techniques for cancer drug discovery. Biology. 2014; 3 (2): 345–367. DOI: 10.3390/biology3020345.
7. Edmondson R., Broglie J.J., Adcock A.F., Yang L. Threedimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay and drug development technologies. 2014; 12 (4): 207–218. DOI: 10.1089/adt.2014.573.
8. Tibbitt M.W., Anseth K.S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnology and bioengineering. 2009; 103 (4): 655–663. DOI: 10.1002/bit.22361.
9. Bi Y.A., Kazolias D., Duignan D.B. Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab. Dispos. 2006; 34: 1658–1665. DOI: 10.1124/dmd.105.009118.
10. Dunn J.C.Y., Tompkins R.G., Yarmush M.L. Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation. J. Cell Biol. 1992; 116 (4): 1043–1053. DOI: 10.1083/jcb.116.4.1043.
11. Ezzell R.M., Toner M., Hendricks K., Dunn J.C., Tompkins R.G., Yarmush M.L.. Effect of collagen gel configuration on the cytoskeleton in cultured rat hepatocytes. Exp. Cell Res. 1993; 208: 442–452. DOI: 10.1006/excr.1993.1266.
12. Jones H.M., Barton H.A., Lai Y., Bi Y.A., Kimoto E., Kempshall S., Tate S.C., El-Kattan A., Houston J.B., Galetin A., Fenner K.S.. Mechanistic pharmacokinetic modeling for the prediction of transporter-mediated disposition in humans from sandwich culture human hepatocyte data. Drug Metab. Dispos. 2012; 40 (5): 1007–1017. DOI: 10.1124/dmd.111.042994.
13. LeCluyse E.L., Audus K.L., Hochman J.H. Formation of extensive canalicular networks by rat hepatocytes cultured in collagen-sandwich configuration. Am. J. Physiol. 1994; 266: C1764–C1774.
14. Price K.J., Tsykin A., Giles K.M., Sladic R.T., Epis M.R., Ganss R., Goodall G.L., Leedman P.J. Matrigel basement membrane matrix influences expression of microRNAs in cancer cell lines. Biochem. Biophys. Res. Commun. 2012; 427 (2): 343–348. DOI: 10.1016/j.bbrc.2012.09.059.
15. Loessner D., Stok K.S., Lutolf M.P., Hutmacher D.W., Clements J.A., Rizzi S.C. Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials. 2010; 31 (32): 8494– 8506. DOI: 10.1016/j.biomaterials.2010.07.064.
16. Luca A.C., Mersch S., Deenen R., Schmidt S., Messner I., Schafer K.L., Baldus S.E., Huckenbeck W., Piekorz R.P., Wolfram T., Knoefel W.T., Krieg A., Stoecklein N.H. Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS One. 2013; 8 (3): e59689. DOI: 10.1371/journal.pone.0059689
17. Shield K., Ackland M.L., Ahmed N., Rice G.E. Multicellular spheroids in ovarian cancer metastases: biology and pathology. Gynecol. Oncol. 2009; 113 (1): 143–148. DOI: 10.1016/j.ygyno.2008.11.032.
18. Zietarska M., Maugard C.M., Filali-Mouhim A., AlamFahmy M., Tonin P.N., Provencher D.M., Mes-Masson A.M. Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC). Mol. Carcinog. 2007; 46 (10): 872–885. DOI: 10.1002/mc.20315.
19. Lee J., Cuddihy M.J., Kotov N.A. Three-dimensional cell culture matrices: state of the art. Tissue Eng. Part B Rev. 2008; 14 (1): 61–86. DOI: 10.1089/teb.2007.0150.
20. Karlsson H., Fryknäs M., Larsson R., Nygren P. Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system. Exper. Cell Res. 2012; 318 (13): 1577–1585. DOI: 10.1016/j.yexcr.2012.03.026.
21. Elliott N.T., Yuan F. A review of three-dimensional in vitro tissue models for drug discovery and transport studies. J. Pharm. Sci. 2010; 100 (1): 59–74. DOI: 10.1002/jps.22257.
22. Walker D.M., Boey G., McDonald L.A. The pathology of oral cancer. Pathology. 2003; 35 (5): 376–383.
23. Trédan O., Galmarini C.M., Patel K., Tannock I.F. Drug resistance and the solid tumor microenvironment. J. Nat. Cancer Inst. 2007; 99 (19): 1441–1454. DOI: 10.1093/jnci/djm135.
24. Sodek K.L., Ringuette M.J., Brown T.J. Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype. Int. J. Cancer. 2009; 124 (9): 2060–2070. DOI: 10.1002/ijc.24188.
25. Yip D., Cho C.H. A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing. Biochem. Biophys. Res. Commun. 2013; 433 (3): 327–332. DOI: 10.1016/j.bbrc.2013.03.008.
26. Gurski L., Petrelli N., Jia X., Farach-Carson M. 3D matrices for anti-cancer drug testing and development. Oncol. Issues. 2010; 25 (1): 20–25.
27. Wen Z., Liao Q., Hu Y., You L., Zhou L., Zhao Y. A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay. Braz. J. Med. Biol. Res. 2013; 46 (7): 634–642. DOI: 10.1590/1414-431X20132647.
28. Tung Y.C., Hsiao A.Y., Allen S.G., Torisawa Y., Ho M., Takayama S. High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst. 2011; 136 (3): 473–478. DOI: 10.1039/c0an00609b.
29. Chitcholtan K., Sykes P., Evans J. The resistance of intracellular mediators to doxorubicin and cisplatin aredistinct in 3D and 2D endometrial cancer. J. Transl. Med. 2012; 10: 1–16. DOI: 10.1186/1479-5876-10-38.
30. Swietach P., Hulikova A., Patiar S., Vaughan-Jones R.D., Harris A.L. Importance of intracellular pH in determining the uptake and efficacy of the weakly basic chemotherapeutic drug, doxorubicin. PLoS One. 2012; 7: e35949.
31. Nam J.M., Onodera Y., Bissell M.J., Park C.C. Breast cancer cells in three-dimensional culture display an enhanced radioresponse after coordinate targeting of integrin α5β1 and fibronectin. Cancer Res. 2010; 70 (13): 5238–5248. DOI: 10.1158/0008-5472.CAN-09-2319.
32. Michaylira C.Z., Wong G.S., Miller C.G., Gutierrez C.M., Nakagawa H., Hammond R., Klein-Szanto A.J., Lee J.S., Kim S.B., Herlyn M., Diehl J.A., Gimotty P, Rustgi A.K. Periostin, a cell adhesion molecule, facilitates invasion in the tumor microenvironment and annotates a novel tumor-invasive signature in esophageal cancer. Cancer Res. 2010; 70 (13): 5281–5292. DOI: 10.1158/0008-5472.CAN-10-0704.
33. Kondo J., Endo H., Okuyama H., Ishikawac O., Iishid H., Tsujiib M., Ohuec M., Inoue M. Retaining cell–cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proc. Natl. Acad. Sci. USA. 2011; 108 (15): 6235–6240. DOI: 10.1073/pnas.1015938108/.
34. Praveen K., Streiner N., Vo M., Anderes K., Yokota K., Ikeya T. Evaluation of Cell-able spheroid culture system for culturing patient derived primary tumor cells. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research. Cancer Res. 2012; 72 (8 Suppl): 5270 [Abstract].
35. Fiebig H: Oncotest. www.oncotest.com/id-3d-assays.html (last accessed on April 11, 2014).
Review
For citations:
Galimova E.S., Galagudza M.М. Two-dimensional and three-dimensional cell culture models in vitro: pros and cons. Bulletin of Siberian Medicine. 2018;17(3):188-196. (In Russ.) https://doi.org/10.20538/1682-0363-2018-3-188-196
Views:
1386
Email this article 