3D tumor model – a platform for anticancer drug development
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Łukasz Kaźmierski
and
Małgorzata Maj
Abstract
While still attractive, the currently available 2D cell culture models present several limitations and if possible should be supplemented with their 3D counterparts, that is with spheroids/organoids or bio-printed structures. Those alternatives can sometimes show widely different results compared to the simpler 2D cell culture, especially during cytotoxicity testing that is often used during cancer drug development and in the rising field of personalized medicine. Although some of the methods like spheroid formation and basic alginate based bio-prints were already available for years, they still require huge amounts of optimization and troubleshooting to be used effectively. Proficient use of dedicated tools and software can help to overcome some of the difficulties associated with those seemingly well described models. In this article we compare the most popular and currently available methods of acquiring 3D bio-models while describing their limitations and shortcomings as well as technical hurdles that one has to overcome to succeed in the use of this complex model.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
References
1. Shoemaker, RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Canc 2006;6:813–23. https://doi.org/10.1038/nrc1951.Search in Google Scholar PubMed
2. Chen, L, Xiao, Z, Meng, Y, Zhao, Y, Han, J, Su, G, et al.. The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. Biomaterials 2012;33:1437–44. https://doi.org/10.1016/j.biomaterials.2011.10.056.Search in Google Scholar PubMed
3. Gardner, E. 3-D printing models, augmented reality images help surgeons visualize tumors. USA: RSNA Daily Bulletin; 2017.Search in Google Scholar
4. Jensen, C, Teng, Y. Is it time to start transitioning from 2D to 3D cell culture? Front Mol Biosci 2020;6:7–33. https://doi.org/10.3389/fmolb.2020.00033.Search in Google Scholar PubMed PubMed Central
5. Tannenbaum, J, Bennett, BT. Russell and Burch’s 3Rs then and now: the need for clarity in definition and purpose. J Am Assoc Lab Anim Sci 2015;54:120–32.Search in Google Scholar
6. Ariadne. New Sci 1974;64:80.Search in Google Scholar
7. Scott Crump, S. U.S. patent no. 005121329; 1989.Search in Google Scholar
8. Almquist, TA, Smalley, DR. U.S. patent no. US5569349A; 1995.Search in Google Scholar
9. Smalley, DR, Vorgitch, TJ, Manners, CR, Hull, CW, VanDorin, SL. U.S. patent no. US5597520A; 1994.Search in Google Scholar
10. Childers, CM, Charles, WH. U.S. patent no. US5609812A; 1993.Search in Google Scholar
11. Charles, WH. U.S. patent no. US5762856A; 1995.Search in Google Scholar
12. Revilla León, M, Klemm, IM, García-Arranz, J, Özcan, M. 3D metal printing – additive manufacturing technologies for frameworks of implant-borne fixed dental prosthesis. Eur J Prosthodont Restor Dent 2017;25:143–7. https://doi.org/10.1922/ejprd_revillaleon05.Search in Google Scholar
13. Lerman, MJ, Lembong, J, Muramoto, S, Gillen, G, Fisher, JP. The evolution of polystyrene as a cell culture material. Tissue Eng B Rev 2018;24:359–72. https://doi.org/10.1089/ten.teb.2018.0056.Search in Google Scholar
14. Leary, E, Rhee, C, Wilks, B, Morgan, JR. Accurate quantitative wide-field fluorescence microscopy of 3-D spheroids. Biotechniques 2016;61:237–47. https://doi.org/10.2144/000114472.Search in Google Scholar PubMed
15. Claudia, M, Kristin, Ö, Jennifer, O, Eva, R, Eleonore, F. Comparison of fluorescence-based methods to determine nanoparticle uptake by phagocytes and non-phagocytic cells in vitro. Toxicology 2017;378:25–36. https://doi.org/10.1016/j.tox.2017.01.001.Search in Google Scholar PubMed PubMed Central
16. Smyrek, I, Stelzer, EH. Quantitative three-dimensional evaluation of immunofluorescence staining for large whole mount spheroids with light sheet microscopy. Biomed Opt Express 2017;8:484–99. https://doi.org/10.1364/boe.8.000484.Search in Google Scholar
17. Lazzari, G, Couvreur, P, Mura, S. Multicellular tumor spheroids: a relevant 3D model for the in vitro preclinical investigation of polymer nanomedicines. Polym Chem 2017;8:4947–69. https://doi.org/10.1039/c7py00559h.Search in Google Scholar
18. Naghieh, S, Sarker, M, Izadifar, M, Chen, X. Dispensing-based bioprinting of mechanically-functional hybrid scaffolds with vessel-like channels for tissue engineering applications – a brief review. J Mech Behav Biomed Mater 2018;78:298–314. https://doi.org/10.1016/j.jmbbm.2017.11.037.Search in Google Scholar PubMed
19. Zeming, G, Jianzhong, F, Hui, L, Yong, H. Development of 3D bioprinting: from printing methods to biomedical applications. Asian J Pharm Sci 2019;15:529–57. https://doi.org/10.1016/j.ajps.2019.11.003.Search in Google Scholar PubMed PubMed Central
20. Gopinathan, J, Noh, I. Recent trends in bioinks for 3D printing. Biomater Res 2018;22:11. https://doi.org/10.1186/s40824-018-0122-1.Search in Google Scholar PubMed PubMed Central
21. Gungor-Ozkerim, PS, Inci, I, Zhang, YS, Khademhosseini, A, Dokmeci, MR. Bioinks for 3D bioprinting: an overview. Biomater Sci 2018;6:915–46. https://doi.org/10.1039/c7bm00765e.Search in Google Scholar PubMed PubMed Central
22. Nie, S, Hsiao, WL, Pan, W, Yang, Z. Thermoreversible Pluronic F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies. Int J Nanomed 2011;6:151–66. https://doi.org/10.2147/IJN.S15057.Search in Google Scholar PubMed PubMed Central
23. Wang, X, Ao, Q, Tian, X, Fan, J, Tong, H, Hou, W, et al.. Gelatin-based hydrogels for organ 3D bioprinting. Polymers 2017;9:401. https://doi.org/10.3390/polym9090401.Search in Google Scholar PubMed PubMed Central
24. Lee, A, Hudson, AR, Shiwarski, DJ, Tashman, JW, Hinton, TJ, Yerneni, S, et al.. 3D bioprinting of collagen to rebuild components of the human heart. Science 2019;365:482–7. https://doi.org/10.1126/science.aav9051.Search in Google Scholar PubMed
25. Köpf, M, Campos, DF, Blaeser, A, Sen, KS, Fischer, H. A tailored three-dimensionally printable agarose-collagen blend allows encapsulation, spreading, and attachment of human umbilical artery smooth muscle cells. Biofabrication 2016;8:025011. https://doi.org/10.1088/1758-5090/8/2/025011.Search in Google Scholar PubMed
26. Wu, D, Yu, Y, Tan, J, Huang, L, Luo, B, Lu, L, et al.. 3D bioprinting of gellan gum and poly (ethylene glycol) diacrylate based hydrogels to produce human-scale constructs with high-fidelity. Mater Des 2018;160:486–95. https://doi.org/10.1016/j.matdes.2018.09.040.Search in Google Scholar
27. Albritton, JL, Miller, JS. 3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments. Dis Model Mech 2017;10:3–14. https://doi.org/10.1242/dmm.025049.Search in Google Scholar PubMed PubMed Central
28. Satyavrata, S, Nikhita, J. 3D printing for the development of in vitro cancer models. Curr Opin Biomed Eng 2017;2:35–42. https://doi.org/10.1016/j.cobme.2017.06.003.Search in Google Scholar
29. Yu, Y, Zhang, Y, Martin, JA, Ozbolat, IT. Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels. J Biomech Eng 2013;135:91011. https://doi.org/10.1115/1.4024575.Search in Google Scholar PubMed PubMed Central
30. Liliang, O. Study on microextrusion-based 3D bioprinting and bioink crosslinking mechanisms. Singapore: Springer; 2019.Search in Google Scholar
31. Mishbak, HH, Cooper, G, Bartolo, PJ. Development and characterization of a photocurable alginate bioink for three-dimensional bioprinting. Int J Bioprint 2019;5:189. https://doi.org/10.18063/ijb.v5i2.189.Search in Google Scholar PubMed PubMed Central
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Articles in the same Issue
- Frontmatter
- Reviews
- Influence of lime (CaO) on low temperature leaching of some types of bauxite from Guinea
- Ethnobotanical survey, phytoconstituents and antibacterial investigation of Rapanea melanophloeos (L.) Mez. bark, fruit and leaf extracts
- Catalytic properties of supramolecular polymetallated porphyrins
- Lignin-based polymers
- Bio-based polyhydroxyalkanoates blends and composites
- Biodegradable poly(butylene adipate-co-terephthalate) (PBAT)
- Repurposing tires – alternate energy source?
- Theoretical investigation of the stability, reactivity, and the interaction of methyl-substituted peridinium-based ionic liquids
- Polymeric membranes for biomedical applications
- Design of locally sourced activated charcoal filter from maize cob for wastewater decontamination: an approach to fight waste with waste
- Synthesis of biologically active heterocyclic compounds from allenic and acetylenic nitriles and related compounds
- Magnetic measurement methods to probe nanoparticle–matrix interactions
- Health and exposure risk assessment of heavy metals in rainwater samples from selected locations in Rivers State, Nigeria
- Evaluation of raw, treated and effluent water quality from selected water treatment plants: a case study of Lagos Water Corporation
- A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products
- Hemicyanine dyes
- Thermodynamics of the micellization of quaternary based cationic surfactants in triethanolamine-water media: a conductometry study
- Compounds isolated from hexane fraction of Alternanthera brasiliensis show synergistic activity against methicillin resistant Staphylococcus aureus
- Internal structures and mechanical properties of magnetic gels and suspensions
- SPIONs and magnetic hybrid materials: Synthesis, toxicology and biomedical applications
- Magnetic field controlled behavior of magnetic gels studied using particle-based simulations
- The microstructure of magnetorheological materials characterized by means of computed X-ray microtomography
- Core-modified porphyrins: novel building blocks in chemistry
- Anticancer potential of indole derivatives: an update
- Novel drug design and bioinformatics: an introduction
- Multi-objective optimization of CCUS supply chains for European countries with higher carbon dioxide emissions
- Exergy analysis of an atmospheric residue desulphurization hydrotreating process for a crude oil refinery
- Development in nanomembrane-based filtration of emerging contaminants
- Supply chain optimization framework for CO2 capture, utilization, and storage in Germany
- Naturally occurring heterocyclic anticancer compounds
- Part-II- in silico drug design: application and success
- Advances in biopolymer composites and biomaterials for the removal of emerging contaminants
- Nanobiocatalysts and photocatalyst in dye degradation
- 3D tumor model – a platform for anticancer drug development
- Hydrogen production via water splitting over graphitic carbon nitride (g-C3N4 )-based photocatalysis
Articles in the same Issue
- Frontmatter
- Reviews
- Influence of lime (CaO) on low temperature leaching of some types of bauxite from Guinea
- Ethnobotanical survey, phytoconstituents and antibacterial investigation of Rapanea melanophloeos (L.) Mez. bark, fruit and leaf extracts
- Catalytic properties of supramolecular polymetallated porphyrins
- Lignin-based polymers
- Bio-based polyhydroxyalkanoates blends and composites
- Biodegradable poly(butylene adipate-co-terephthalate) (PBAT)
- Repurposing tires – alternate energy source?
- Theoretical investigation of the stability, reactivity, and the interaction of methyl-substituted peridinium-based ionic liquids
- Polymeric membranes for biomedical applications
- Design of locally sourced activated charcoal filter from maize cob for wastewater decontamination: an approach to fight waste with waste
- Synthesis of biologically active heterocyclic compounds from allenic and acetylenic nitriles and related compounds
- Magnetic measurement methods to probe nanoparticle–matrix interactions
- Health and exposure risk assessment of heavy metals in rainwater samples from selected locations in Rivers State, Nigeria
- Evaluation of raw, treated and effluent water quality from selected water treatment plants: a case study of Lagos Water Corporation
- A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products
- Hemicyanine dyes
- Thermodynamics of the micellization of quaternary based cationic surfactants in triethanolamine-water media: a conductometry study
- Compounds isolated from hexane fraction of Alternanthera brasiliensis show synergistic activity against methicillin resistant Staphylococcus aureus
- Internal structures and mechanical properties of magnetic gels and suspensions
- SPIONs and magnetic hybrid materials: Synthesis, toxicology and biomedical applications
- Magnetic field controlled behavior of magnetic gels studied using particle-based simulations
- The microstructure of magnetorheological materials characterized by means of computed X-ray microtomography
- Core-modified porphyrins: novel building blocks in chemistry
- Anticancer potential of indole derivatives: an update
- Novel drug design and bioinformatics: an introduction
- Multi-objective optimization of CCUS supply chains for European countries with higher carbon dioxide emissions
- Exergy analysis of an atmospheric residue desulphurization hydrotreating process for a crude oil refinery
- Development in nanomembrane-based filtration of emerging contaminants
- Supply chain optimization framework for CO2 capture, utilization, and storage in Germany
- Naturally occurring heterocyclic anticancer compounds
- Part-II- in silico drug design: application and success
- Advances in biopolymer composites and biomaterials for the removal of emerging contaminants
- Nanobiocatalysts and photocatalyst in dye degradation
- 3D tumor model – a platform for anticancer drug development
- Hydrogen production via water splitting over graphitic carbon nitride (g-C3N4 )-based photocatalysis
