![3D cell culture and anticancer drug testing | Cherry Biotech 2019 Cherry Biotech. viewed 8 May 2019, <https://www.cherrybiotech.com/scientific-
note/organs-on-chip/3d-cell-culture-and-anticancer-drug-testing>.
Bing He, Guomin Chen, Yi Zeng, 2016: Three-dimensional cell culture models for investigating human viruses, Virologica Sinica, 31, 363-379.,
viewed 08 May 2019, <https://www.virosin.org/article/doi/10.1007/s12250-016-3889-z#bpampaloni2007>
Bourré, L., 2018. Facilitating Drug Discovery with 3D In Vitro Oncology Models. [online] Blog.crownbio.com. Available at:
https://blog.crownbio.com/in-vitro-3d-organoids-spheroids-oncology [Accessed 3 May 2019].
Breslin, S & O’Driscoll, L 2013, "Three-dimensional cell culture: the missing link in drug discovery", Drug Discovery Today, vol. 18, no. 5-6, pp.
240-249. viewed 1 May 2019, <https://www.ncbi.nlm.nih.gov/pubmed/23073387>.
Duval, K., Grover, H., Han, L. H., Mou, Y., Pegoraro, A. F., Fredberg, J., & Chen, Z., 2017. “Modeling Physiological Events in 2D vs. 3D Cell
Culture.”, Physiology (Bethesda, Md.), 32(4), 266–277., viewed 08 May 2019,
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545611/?report=classic>
Gurski, L.A., Petrelli, N.J., Jia, X. and Farach-Carson, M.C., 2010. 3D matrices for anti-cancer drug testing and development. Oncology Issues,
25(1), pp.20-25.
Huang, L, Holtzinger, A, Jagan, I, BeGora, M, Lohse, I, Ngai, N, Mutuswamy LB, Crawford, HC, Arrowsmith, C, Kalloger, SE, Renouf, DJ,
Connor, AA, Clearly, S, Schaeffer, DF, Roehrl, M, Tsao MS, Gallinger, S, Keller, G & Muthuswamy, SK 2015, “Ductal pancreatic cancer
modeling and drug screening using human pluripotent stem cell– and patient-derived tumor organoids.” Nature Medicine, vol. 21, no. 11, pp.
1364–1371, viewed 08 May 2019, <https://www.nature.com/articles/nm.3973>
REFERENCES](https://image.slidesharecdn.com/animalbiotechcasestudy-190509113210/85/Potentials-of-3D-models-in-anticancer-drug-screening-10-320.jpg)
![Nibib.nih.gov. (2019). 3D bioprinted cancer model to test anticancer drugs | National Institute of Biomedical Imaging and
Bioengineering. [online] Available at: https://www.nibib.nih.gov/news-events/newsroom/3d-bioprinted-cancer-model-test-anticancer-
drugs [Accessed 9 May 2019].
Souza, GR, Molina, JR, Raphael, RM, Ozawa, MG, Stark, DJ, Levin, CS, Bronk, LF, Ananta, JS, Mndelin, J, Georgescu, M, Bankson, JA,
Gelovani, JG, Killian, TC, Arap, W & Pasqualini, R 2010, “Three-dimensional tissue culture based on magnetic cell levitation.” Nature
Nanotechnology, vol. 5, no.4, pp. 291–296, viewed 08 May 2019, <https://www.nature.com/articles/nnano.2010.23>
Tung, YC, Hsiao, AY, Allen, SG, Torisawa, Y, Ho, M, & Takayama, S 2011, “High-throughput 3D spheroid culture and drug testing using a 384
hanging drop array.” The Analyst, vol. 136, no. 3, pp. 473–478, viewed 08 May 2019,
<https://pubs.rsc.org/en/content/articlelanding/2011/an/c0an00609b/unauth#!divAbstract>
Zanoni, M., Pignatta, S., Arienti, C., Bonafè, M. and Tesei, A., 2019. Anticancer drug discovery using multicellular tumor spheroid
models. Expert Opinion on Drug Discovery, 14(3), pp.289-301.](https://image.slidesharecdn.com/animalbiotechcasestudy-190509113210/85/Potentials-of-3D-models-in-anticancer-drug-screening-12-320.jpg)
Potentials of 3D models in anticancer drug screening
- 2. In the quest of successfully launching a new drug, drug discovery in the preclinical phase, and drug development in the clinical phase is crucial. Especially in the field of anti cancer drug screening, researchers have been heavily involved in producing new drugs that bridge the gap between experimental research and clinical trials (Meng et al., 2019). Recent advancement in bioprinting, has thus produced several in vitro models such as 2D and 3D models that are widely used in drug screening. 2D models are traditionally used by researchers to evaluate effectiveness of anti-cancer drugs towards cancer cell lines. Additionally, it is to understand the molecular pathways of cell proliferation. 2D models are also grown in either shake flasks or Petri dishes with growth medium as their source of nutrients (Breslin & O’Driscoll, 2013). Meanwhile, in this presentation, 3D models are used by researchers to mimic tumour microenvironment and visualise the structure of cells (Breslin & O’Driscoll, 2013). This presentation will be reviewing the differences between these two models, the recent preference of researchers for 3D models, and case study that highlights the new direction for the future 3D bioprinted models. INTRODUCTION
- 3. COMPARISON OF 2D AND 3D MODELS 2D 3D
- 4. 3D models mimic in vivo physiology of organisms, such as the histological architecture and heterogeneity (Jackson and Lu, 2016). They mimic native matrixes and cell-cell interaction as well as the interactions with the extracellular matrix (ECM) (Leong and Ng, 2014). Researchers prefer 3D models because 2D models are unnatural while animal models are expensive and brings about ethical issues (Gurski et al., 2010). Cancer cells cultured in 3D models reflects the behaviour of cancer cells in their native, in vivo environment (Gurski et al., 2010) An example would be where cancer cells cultured in 3D models respond to chemotherapeutic treatments similarly to in vivo cancer cells. WHY RESEARCHERS ARE USING 3D MODELS Source: (Bourré, 2018)
- 6. Other methods of generating 3D tumour models Methods of anticancer drug screening from 3D tumour models •Once the 3D tumour models have been cultured in anticancer drug supplied medium, different analysis techniques are used to screen for the most efficient drug.
- 7. 3D bioprinted cancer model to test anticancer drugs A new direction in producing 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments Source:National Institute of Biomedical Imaging and Bioengineering (NBIB),2019. A NIBIB-funded research conducted recently by a team of researchers from University of Minnesota (UMN), has developed a newly dynamic and efficient 3D bioprinted tumor model for anticancer drug screening. The 3D model was made in a laboratory dish, and functions in studying the primary site, growth and spread of cancer tumours in the body. Thus, tackling the recurring problems in which previous 2D models, could not replicate the conditions and outcomes of tumor growth in the human body. The 3D bioprinting technology used in this project originated from UMN lab through Michael McAlpine. Through this research, 3D printed biochemical capsules were combined with 3D bioprinted tumor cells. Through 3D bioprinting technology, melanoma cancer cells,lung cancer cells, normal cells, and blood-vessel like structures, are able to be precisely located in the laboratory dish based on their individual functions (Nibib.nih.gov, 2019).
- 8. Chemicals that guide cancer cell migration or the growth of blood vessels, are as well packed in the cores of hydrogels. They are also encapsulated within an outer shell made of gold nanorods. A time controlled release of the capsules are activated by laser light, which then creates a chemical gradient that ultimately guides targeted cell growth. Thus, these features provides a 4D control over both space and time. “The cells and capsules are precisely printed in biologically relevant sites and the chemical depots propel movement upon a triggered release. This is a dynamic 3D tissue engineering system giving the user control over the diffusion process at some later point after the printing process.” emphasized McAlpine (Nibib.nih.gov, 2019). Figure above shows the schematics of the 3D bioprinted in vitro tumor model, which demonstrates the integration of tumor cells, the blood- vessel like structures, and chemical gradients 3D bioprinted cancer model to test anticancer drugs A new direction in producing 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments Source: Nibib.nih. gov, 2019).
- 9. CONCLUSION (Zanoni et al., 2019) (Zanoni et al., 2019)
- 10. 3D cell culture and anticancer drug testing | Cherry Biotech 2019 Cherry Biotech. viewed 8 May 2019, <https://www.cherrybiotech.com/scientific- note/organs-on-chip/3d-cell-culture-and-anticancer-drug-testing>. Bing He, Guomin Chen, Yi Zeng, 2016: Three-dimensional cell culture models for investigating human viruses, Virologica Sinica, 31, 363-379., viewed 08 May 2019, <https://www.virosin.org/article/doi/10.1007/s12250-016-3889-z#bpampaloni2007> Bourré, L., 2018. Facilitating Drug Discovery with 3D In Vitro Oncology Models. [online] Blog.crownbio.com. Available at: https://blog.crownbio.com/in-vitro-3d-organoids-spheroids-oncology [Accessed 3 May 2019]. Breslin, S & O’Driscoll, L 2013, "Three-dimensional cell culture: the missing link in drug discovery", Drug Discovery Today, vol. 18, no. 5-6, pp. 240-249. viewed 1 May 2019, <https://www.ncbi.nlm.nih.gov/pubmed/23073387>. Duval, K., Grover, H., Han, L. H., Mou, Y., Pegoraro, A. F., Fredberg, J., & Chen, Z., 2017. “Modeling Physiological Events in 2D vs. 3D Cell Culture.”, Physiology (Bethesda, Md.), 32(4), 266–277., viewed 08 May 2019, <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545611/?report=classic> Gurski, L.A., Petrelli, N.J., Jia, X. and Farach-Carson, M.C., 2010. 3D matrices for anti-cancer drug testing and development. Oncology Issues, 25(1), pp.20-25. Huang, L, Holtzinger, A, Jagan, I, BeGora, M, Lohse, I, Ngai, N, Mutuswamy LB, Crawford, HC, Arrowsmith, C, Kalloger, SE, Renouf, DJ, Connor, AA, Clearly, S, Schaeffer, DF, Roehrl, M, Tsao MS, Gallinger, S, Keller, G & Muthuswamy, SK 2015, “Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell– and patient-derived tumor organoids.” Nature Medicine, vol. 21, no. 11, pp. 1364–1371, viewed 08 May 2019, <https://www.nature.com/articles/nm.3973> REFERENCES
- 11. Ivascu, A & Kubbies, M 2006, “Rapid Generation of Single-Tumor Spheroids for High-Throughput Cell Function and Toxicity Analysis”, SLAS Discovery, vol. 11, no. 8, pp. 922-932, viewed 08 May 2019, <https://journals.sagepub.com/doi/abs/10.1177/1087057106292763> Jackson, E.L. and Lu, H., 2016. Three-dimensional models for studying development and disease: moving on from organisms to organs-on-a- chip and organoids. Integrative Biology, 8(6), pp.672-683. Jitcy Saji Joseph, Sibusiso Tebogo Malindisa and Monde Ntwasa, 2018, Two Dimensional (2D) and Three Dimensional(3D) Cell Culturing in Drug Discovering”, Intechopen, viewed 08 May 2019, <https://www.intechopen.com/books/cell-culture/two-dimensional-2d-and-three- dimensional-3d-cell-culturing-in-drug-discovery> Kwapiszewska, K, Michalczuk, A, Rybka, M, Kwapiszewski, R & Brzózka, Z 2014, “A microfluidic-based platform for tumour spheroid culture, monitoring and drug screening”, Lab Chip, vol. 14, pp. 2096-2104, <https://pubs.rsc.org/en/content/articlehtml/2014/lc/c4lc00291a> Leong, D.T. and Ng, K.W., 2014. Probing the relevance of 3D cancer models in nanomedicine research. Advanced drug delivery reviews, 79, pp.95-106. Markovitz-Bishitz, Y, Tauber, Y, Afrimzon, E, Zurgil, N, Sobolev, M, Shafran, Y, Deutsch, A, Howitz, S, Deutsch, M 2010, “A polymer microstructure array for the formation, culturing, and high throughput drug screening of breast cancer spheroids.” Biomaterials, vol. 31, no. 32, pp. 8436–8444, viewed 08 May 2019, <https://www.sciencedirect.com/science/article/pii/S0142961210008938> Marta Kapałczyńska , Tomasz Kolenda, Weronika Przybyła, et al., 2016, “2D and 3D cell cultures – a comparison of different types of cancer cell cultures”, 14, 4: 910–919, viewed 08 May 2019, <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040128/pdf/AMS-14-28752.pdf> Mellor, HR, Ferguson, DJ & Callaghan, R 2005, “A model of quiescent tumour microregions for evaluating multicellular resistance to chemotherapeutic drugs”, British Journal of Cancer, vol. 93, pp. 302-309, viewed 08 May 2019, <https://www.nature.com/articles/6602710>
- 12. Nibib.nih.gov. (2019). 3D bioprinted cancer model to test anticancer drugs | National Institute of Biomedical Imaging and Bioengineering. [online] Available at: https://www.nibib.nih.gov/news-events/newsroom/3d-bioprinted-cancer-model-test-anticancer- drugs [Accessed 9 May 2019]. Souza, GR, Molina, JR, Raphael, RM, Ozawa, MG, Stark, DJ, Levin, CS, Bronk, LF, Ananta, JS, Mndelin, J, Georgescu, M, Bankson, JA, Gelovani, JG, Killian, TC, Arap, W & Pasqualini, R 2010, “Three-dimensional tissue culture based on magnetic cell levitation.” Nature Nanotechnology, vol. 5, no.4, pp. 291–296, viewed 08 May 2019, <https://www.nature.com/articles/nnano.2010.23> Tung, YC, Hsiao, AY, Allen, SG, Torisawa, Y, Ho, M, & Takayama, S 2011, “High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array.” The Analyst, vol. 136, no. 3, pp. 473–478, viewed 08 May 2019, <https://pubs.rsc.org/en/content/articlelanding/2011/an/c0an00609b/unauth#!divAbstract> Zanoni, M., Pignatta, S., Arienti, C., Bonafè, M. and Tesei, A., 2019. Anticancer drug discovery using multicellular tumor spheroid models. Expert Opinion on Drug Discovery, 14(3), pp.289-301.