Open Access
Subscription Access
Dynamic Three-Dimensional Cell-Culture Systems for Enhanced in Vitro Applications
The advent of dynamic three-dimensional cell cultures has transformed the field of biological research as they bridge the gap between in vitro and in vivo systems. 3D cell-culture techniques can be categorized into two types: static and dynamic culture systems. Traditional cell-culture models are considered to be ‘static’ in nature, as the cells are grown on matrices or scaffolds with little focus given to the complexity of the growth conditions that exist in the in vivo tissue microenvironments (presence of continuous blood supply for the development of tumour vasculature). Thus, static 3D cultures do not accurately mimic in vivo cellular architecture and function. The development of a ‘dynamic’ culture environment has offered 3D culture models with the potential to improve the ‘naturalness’ of the cells being cultured and thereby have more in vivo relevance for translational research. This makes them relatively more superior than single cell-type static 3D cell cultures. Dynamic systems include magnetic- and acoustic-based assembly devices, micropocket cultures, dielectrophoretic and microfluidic platforms. Microfluidic devices might be the most versatile of these culture platforms, considering their engineering diversity, their potential to improve molecular crosstalk among culture elements and their prospective range of applications.
Keywords
In Vitro Applications, Scaffold-Based and Scaffold-Free Systems, Static and Dynamic Culture Systems, Three-dimensional Cell Culture.
User
Font Size
Information
- Amelian, A., Wasilewska, K., Megias, D. and Winnicka, K., Application of standard cell cultures and 3D in vitro tissue models as an effective tool in drug design and development. Pharmacol. Rep., 2017, 69(5), 861–870.
- Edmondson, R., Broglie, J. J., Adcock, A. F. and Yang, L., Threedimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev. Technol., 2014, 12(4), 207–218.
- Langhans, S. A., Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front. Pharmacol., 2018, 9(6), 1–14.
- Hoarau-Véchot, J., Rafii, A., Touboul, C. and Pasquier, J., Halfway between 2D and animal models: are 3D cultures the ideal tool to study cancer-microenvironment interactions? Int. J. Mol. Sci., 2018, 19(1), 181.
- Mark, I. W., Evaniew, N. and Ghert, M., Lost in translation: animal models and clinical trials in cancer treatment. Am. J. Transl. Res., 2014, 6, 114–118.
- Souza, A. G. et al., Comparative assay of 2D and 3D cell culture models: proliferation, gene expression and anticancer drug response. Curr. Pharm. Des., 2018, 24(15), 1689–1694.
- Maddaly, R., Paramesh, V., Kaviya, S. R. and Anuradha, E., Solomon FDP 3D cell culture systems: advantages and applications. J. Cell. Physiol., 2015, 230(1), 16–26.
- Imamura, Y. et al., Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer. Oncol. Rep., 2015, 33(4), 1837–1843.
- Costa, E. C., Moreira, A. F., de Melo-Diogo, D., Gaspar, V. M., Carvalho, M. P. and Correia, I. J., 3D tumor spheroids: an overview on the tools and techniques used for their analysis. Biotechnol. Adv., 2016, 34(8), 1427–1441.
- Chaicharoenaudomrung, N., Kunhorm, P. and Noisa, P., Threedimensional cell culture systems as an in vitro platform for cancer and stem cell modelling. World J. Stem Cells, 2019, 11(12), 1065–1083.
- Kapałczyńska, M. et al., 2D and 3D cell cultures – a comparison of different types of cancer cell cultures. Arch. Med. Sci., 2018, 14(4), 910–919.
- Chen, C., Townsend, A. D., Hayter, E. A., Birk, H. M., Sell, S. A. and Martin, R. S., Insert-based microfluidics for 3D cell culture with analysis. Anal. Bioanal. Chem., 2018, 410(12), 3025–3035.
- Wu, Q. et al., Organ-on-a-chip: recent breakthroughs and future prospects. BioMed. Eng. OnLine, 2020, 19, 9.
- Jensen, C. and Teng, Y., Is it time to start transitioning from 2D to 3D cell culture? Front. Mol. Biosci., 2020, 7, 33.
- Yuan, H., Xing, K. and Hsu, H. Y., Trinity of three-dimensional (3D) scaffold, vibration and 3D printing on cell culture application: a systematic review and indicating future direction. Bioengineering (Basel), 2018, 5(3), 57.
- Burdick, J. A. and Murphy, W. L., Moving from static to dynamic complexity in hydrogel design. Nature Commun., 2012, 3(1269), 1–8.
- Alghuwainem, A., Alshareeda, A. T. and Alsowayan, B., Scaffoldfree 3-D cell sheet technique bridges the gap between 2D cell culture and animal models. Int. J. Mol. Sci., 2019, 20(19), 4926.
- Antoni, D., Burckel, H., Ejosset, E. and Noel, G., Three-dimensional cell culture: a breakthrough in vivo. Int. J. Mol. Sci., 2015, 16(3), 5517–5527.
- Haycock, J. W., 3D cell culture: a review of current approaches and techniques. Methods Mol. Biol., 2011, 695, 1–15.
- Chaudhuri, O. et al., Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nature Mater., 2016, 15(3), 326–334.
- Chan, B. P. and Leong, K. W., Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur. Spine J., 2008, 17 (Suppl. 4), 467–479.
- Subramaniyan, A. and Maddaly, R., Agarose hydrogel induced MCF‐7 and BMG‐1 cell line progressive 3D and 3D revert cultures. J. Cell. Physiol., 2018, 233(4), 2768–2772.
- Lelièvre, S. A., Kwok, T. and Chittiboyina, S., Architecture in 3D cell culture: an essential feature for in vitro toxicology. Toxicol. in Vitro. 2017, 45(Pt 3), 287–295.
- Han, H. W., Hou, Y. T. and Hsu, S. H., Angiogenic potential of cospheroids of neural stem cells and endothelial cells in injectable gelatin-based hydrogel. Mater. Sci. Eng. C, 2019, 99, 140– 149.
- Lembong, J., Lerman, M. J., Kingsbury, T. J., Civin, C. I. and Fisher, J. P., A fluidic culture platform for spatially patterned cell growth, differentiation and cocultures. Tissue Eng. – Part A, 2018, 24(23–24), 1715–1732.
- Yaman, S., Anil-Inevi, M., Ozcivici, E. and Tekin, H. C., Magnetic force-based microfluidic techniques for cellular and tissue bioengineering. Front. Bioeng. Biotechnol., 2018, 6, 192.
- Parfenov, V. A. et al., Scaffold-free, label-free and nozzle-free biofabrication technology using magnetic levitational assembly. Biofabrication, 2018, 10(3), 034104.
- Whatley, B. R., Li, X., Zhang, N. and Wen, X., Magnetic‐directed patterning of cell spheroids. J. Biomed. Mater. Res. Part A, 2014, 102(5), 1537–1547.
- Zhao, W. et al., Label-free and continuous-flow ferrohydrodynamic separation of HeLa cells and blood cells in biocompatible ferrofluids. Adv. Funct. Mater., 2016, 26(22), 3990–3998.
- Zhao, W. et al., Label-free ferrohydrodynamic cell separation of circulating tumor cells. Lab. Chip., 2017, 17(18), 3097–3111.
- Zhang, H., Chang, H. and Neuzil, P., DEP-on-a-chip: dielectrophoresis applied to microfluidic platforms. Micromachines (Basel), 2019, 10(6), 423.
- Xu, F. et al., The assembly of cell-encapsulating microscale hydrogels using acoustic waves. Biomaterials, 2011, 32(31), 7847–7855.
- Collins, D. J., O’Rorke, R., Neild, A., Han, J. and Ai, Y., Acoustic fields and microfluidic patterning around embedded microstructures subject to surface acoustic waves. Soft Matter, 2019, 15, 8691–8705.
- Ding, X. et al., Surface acoustic wave microfluidics. Lab. Chip., 2013, 13, 3626–3649.
- Zhao, L., Mok, S. and Moraes, C., Micropocket hydrogel devices for all-in-one formation, assembly, and analysis of aggregatebased tissues. Biofabrication, 2019, 11(4), 045013.
- Carr, S. D., Green, V. L., Stafford, N. D. and Greenman, J., Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices. J. Otolaryngol. Head Neck Surg., 2014, 150, 73.
- Gale, B., Jafek, A., Lambert, C., Goenner, B., Moghimifam, H., Nze, U. and Kamarapu, S. A., Review of current methods in microfluidic device fabrication and future commercialization prospects. Inventions, 2018, 3, 60.
- Jodat, Y. A. et al., Human-derived organ-on-a-chip for personalized drug development. Curr. Pharm. Des., 2018, 24(25), 5471–5486.
- Duffy, D. C., McDonald, J. C., Schueller, O. J. A. and Whitesides, G. M., Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal. Chem., 1998, 70, 4974–4984.
- Ziolkowska, K., Jedrych, E., Kwapiszewski, R., Lopacinska, J., Skolimowski, M. and Chudy, M., PDMS/glass microfluidic cell culture systemfor cytotoxicity tests and cell passage. Sensor. Actuat. B, 2010, 145(1), 533–542.
- Friend, J. and Yeo, L., Fabrication of microfluidic devices using polydimethylsiloxane. Biomicrofluidics, 2010, 4(2), 1–5.
- Chen, W. et al., Nanoroughened adhesion-based capture of circulating tumor cells with heterogenous expression and metastatic characteristics. BMC Cancer, 2016, 16(614), 1–12.
- Qian, C. et al., Clinical significance of circulating tumor cells from lung cancer patients using microfluidic chip. Clin. Exp. Med., 2018, 18, 191–202.
- Hosseini, S. A. et al., Cancer diagnosis: nanoelectromechanical chip (NELMEC) combination of nanoelectronics and microfluidics to diagnose epithelial and mesenchymal circulating tumor cells from leukocytes. Small, 2016, 12, 883–891.
- Pollet, A. M. A. O. and Toonder, J. M. J., Recapitulating the vasculature using organ-on-chip technology. Bioengineering (Basel, Switzerland), 2020, 7(1), 17.
- Kong, J. et al., A novel microfluidic model can mimic organspecific metastasis of circulating tumor cells. Oncotarget, 2016, 7(48), 78421–78432.
- Tang, M., Wang, G., Kong, S. K. and Ho, H. P., A review of biomedical centrifugal microfluidic platforms. Micromachines, 2016, 7(2), 1–29.
- Pauty, J. et al., A vascular endothelia growth factor-dependent sprouting angiogenesis assay based on an in vitro human blood vessel model for the study of anti-angiogenic drugs. EBioMedicine, 2018, 27, 225–236.
- Wijdeven, R., Ramstad, O. H., Bauer, U. S., Halaas, O., Sandvig, A. and Sandvig, I., Structuring a multi-nodal neural network in-vitro within a novel design microfluidic chip. Biomed. Microdevices, 2018, 20(1), 9.
- Courte, R., Renault, A., Jan, J. L., Viovy, J. M., Peyrin, C. and Villard, C., Reconstruction of directed neuronal networks in a microfluidic device with asymmetric microchannels. Methods Cell Biol., 2018, 148, 71–95.
- Osaki, T., Shin, Y., Sivathanu, V., Campisi, M. and Kamm, R. D., In vitro microfluidic models for neurodegenerative disorders. Adv. Healthc. Mater., 2018, 7(2).
- Cho, H. et al., Three-dimensional blood-brain barrier model for in vitro studies of neurovascular. Pathology. Sci. Rep., 2015, 5(15222), 1–9.
- Modarres, H. P. et al., In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain. J. Control Release, 2018, 273, 108–130.
- Brown, T. D. et al., A microfluidic model of human brain (μHuB) for assessment of blood brain barrier. Bioeng. Transl. Med., 2019, 4(2), 1–13.
- Shin, Y. et al., Blood-brain barrier dysfunction in a 3D in vitro model of Alzheimer’s disease. Adv. Sci. (Weinh), 2019, 6(20), 1–10.
- Miccoli, B., Braeken, D. and Li, Y. C. E., Barin-on-a-chip devices for drug screening and disease modeling applications. Curr. Pharm. Des., 2018, 24(45), 5419–5436.
- Marsano, A. et al., Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues. Lab Chip, 2016, 16(3), 599–610.
- Parsa, H., Wang, B. Z. and Vunjak-Novakovic, G., A microfluidic platform for the high-throughput study of pathological cardiac hypertrophy. Lab Chip, 2017, 17(19), 3264–3271.
- Lee, G., Lee, J., Kim, J., Choi, H. S., Kim, J., Lee, S. and Lee, H., Single microfluidic electrochemical sensor system for simultaneous multi-pulmonary hypertension biomarker analyses. Sci. Rep., 2017, 7(1), 1–8.
- Su, T. et al., Cardiac stem cell patch integrated with microengineered blood vessels promotes cardiomyocyte proliferation and neovascularization after acute myocardial infarction. ACS Appl. Mater. Interfaces, 2018, 10(39), 33088–33096
- Sakolish, C. M., Philip, B. and Mahler, G. J., A human proximal tubule-on-a-chip to study renal disease and toxicity. Biomicrofluidics, 2019, 13, 014107.
- Qu, Y., An, F., Luo, Y., Lu, Y., Liu, T., Zhao, W. and Lin, B., A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity. Biomaterials, 2018, 155, 41–53.
- Yin, L., Du, G., Zhang, B., Zhang, H., Yin, R., Zhang, W. and Yang, S. M., Efficient drug screening and nephrotoxicity assessment on co-culture microfluidic kidney chip. Sci. Rep., 2020, 10(1), 1–11.
- Jastrzebska, E., Zuchowska, A., Flis, S., Sokolowska, P., Bulka, M., Dybko, A. and Brzozka, Z., Biological characterization of the modified poly(dimethylsiloxane) surfaces based on cell attachment and toxicity assays. Biomicrofluidics, 2018, 12(4), 044105.
- Carreras, P., Gonzalez, I., Gallardo, M., Ortiz-Ruiz, A. and MartinezLopez, J., Droplet microfluidics for the ex vivo expansion of human primary multiple myeloma cells. Micromachines (Basel), 2020, 11(3), 1–9.
- De Lora, J. A., Velasquez, J. L., Carroll, N. J., Freyer, J. P. and Shreve, A. P., Centrifugal generation of droplet-based 3D cell cultures. SLAS Technol., 2020, 25(5), 436–445.
- Nasseri, B., Soleimani, N., Rabiee, N., Kalbasi, A., Karimi, M. and Hamblin, M. R., Point-of-care microfluidic devices for pathogen detection. Biosens. Bioelectron., 2018, 117, 112–128.
- Krokhine, S., Torabi, H., Doostmohammadi, A. and Rezai, P., Conventional and microfluidic methods for airborne virus isolation and detection. Colloids Surf B, 2021, 206, 111962.
- Han, X., Liu, Y., Yin, J., Yue, M. and Mu, Y., Microfluidic devices for multiplexed detection of foodborne pathogens. Food Res. Int., 2021, 143, 110246.
- Kumar, S., Nehra, M., Mehta, J., Dilbaghi, N., Marrazza, G. and Kaushik, A., Point-of-care strategies for detection of waterborne pathogens. Sensors (Basel), 2019, 19(20), 4476.
- Peyravian, N., Malekzadeh Kebria, M., Kiani, J., Brouki Milan, P. and Mozafari, M., CRISPR-associated (CAS) effectors delivery via microfluidic cell-deformation chip. Mater. (Basel, Switzerland), 2021, 14(12), 3164.
- Han, X. et al., CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation. Sci. Adv., 2015, 1(7), e1500454.
- Li, X., Aghaamoo, M., Liu, S., Lee, D. H. and Lee, A. P., Lipoplexmediated single-cell transfection via droplet microfluidics. Small, 2018, 14(40), e1802055.
- Ashraf, M. N., Asghar, M. W., Rong, Y., Doschak, M. R. and Kiang, T., Advanced in vitro HepaRG culture systems for xenobiotic metabolism and toxicity characterization. Eur. J. Drug Metab. Pharmacokinet., 2019, 44, 437–458.
- Salehi, H., Razavi, S., Esfandiari, E., Kazemi, M., Amini, S. and Amirpour, N., Application of hanging drop culture for retinal precursorlike cells differentiation of human adipose-derived stem cells using small molecules. J. Mol. Neurosci., 2019, 69, 597– 607.
- Foty, R., A simple hanging drop cell culture protocol for generation of 3D spheroids. J. Vis. Exp., 2011, 51, 1–4.
- Tung, Y. C., Hsiao, A. Y., Allen, S. G., Torisawa, Y. S., Ho, M. and Takayama, S., High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst, 2011, 136(3), 473–478.
- Greuel, S. et al., Effect of inoculum density on human-induced pluripotent stem cell expansion in 3D bioreactors. Cell Prolif., 2019, 53(4), 1–12.
- Phelan, M. A., Gianforcaro, A. L., Gerstenhaber, J. A. and Lelkes, P. I., An air-bubble isolating rotating wall vessel bioreactor for improved spheroid/organoid formation. Tissue Eng. Part C, 2019, 25(8), 479–488.
- Amaral, R. L. F., Miranda, M., Marcato, P. D. and Swiech, K., Comparative analysis of 3D bladder tumor spheroids obtained by forced floating and hanging drop methods for drug screening. Front. Physiol., 2017, 89(605), 1–15.
- Breslin, S. and O’Driscoll, L., Three-dimensional cell culture: the missing link in drug discovery. Drug Discov. Today, 2013, 18(5–6), 240–249.
- Souza, G. R. et al., Three-dimensional tissue culture based on magnetic cell levitation. Nat. Nanotechnol., 2010, 5(4), 291–296.
- Haisler, W., Timm, D., Gage, J., Tseng, H., Killian, T. C. and Souza, G. R., Three-dimensional cell culturing by magnetic levitation. Nature Protoc., 2013, 8, 1940–1949.
- Tseng, H., Gage, J. A., Raphael, R. M., Moore, R. H., Killian, T. C., Grande-Allen, K. J. and Souza, G. R., Assembly of a threedimensional multitype bronchiole co-culture model using magnetic levitation. Tissue Eng. Part C, 2013, 19(9), 665.
- Conde, J. P., Madaboosi, N., Soares, R. R., Fernandes, J. T., Novo, P., Moulas, G. and Chu, V., Lab-on-chip systems for integrated bioanalyses. Essays Biochem., 2016, 60(1), 121–131.
- Park, J., Lee, G. H., Yull, P. J., Lee, J. C. and Kim, H. C., Hypergravityinduced multicellular spheroid generation with different morphological patterns precisely controlled on a centrifugal microfluidic platform. Biofabrication, 2017, 9, 045006.
- Christopher, G. F. and Anna, S. L., Microfluidic methods for generating continuous droplet streams. J. Phys. D: Appl. Phys., 2007, 40(19), R319.
- Alessandri, K. et al., Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro. Proc. Natl. Acad. Sci. USA, 2013, 110(37), 14843–14848.
- Sabhachandani, P., Motwani, V., Cohen, N., Sarkar, S., Torchilin, V. and Konry, T., Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform. Lab Chip., 2016, 16(3), 497–505.
- Yu, Y., Wen, H., Ma, J., Lykkemark, S., Xu, H. and Qin, J., Flexible fabrication of biomimetic bamboo-like hybrid microfibers. Adv. Mater., 2014, 26(16), 2494–2499.
- Bawazer, L. A. et al., Combinatorial microfluidic droplet engineering for biomimetic material synthesis. Sci. Adv., 2016, 2(10), e1600567.
- Gao, Y. et al., A versatile valve-enabled microfluidic cell coculture platform and demonstration of its applications to neurobiology and cancer biology. Biomed. Microdevices, 2011, 13(3), 539–548.
- Bhatia, S. N. and Ingber, D. E., Microfluidic organ-on-chips. Nature Biotechnol., 2014, 32(8), 760–772.
- Huh, D. et al., A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med., 2012, 4(159), 159ra147.
- Park, B. H. et al., An integrated rotary microfluidic system with DNA extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-of-care pathogen diagnostics. Biosens. Bioelectron., 2017, 91, 334–340.
- Azizi, M., Zaferani, M., Cheong, S. H. and Abbaspourrad, A., Pathogenic bacteria detection using RNA-based loop-mediated isothermal–amplification–assisted nucleic acid amplification via droplet microfluidics. ACS Sens., 2019, 4(4), 841–848.
- Zhang, Z., Zhao, S., Hu, F., Yang, G., Li, J., Tian, H. and Peng, N., An LED-driven AuNPs-PDMS microfluidic chip and integrated device for the detection of digital loop-mediated isothermal DNA amplification. Micromachines (Basel), 2020, 11(2), 177.
- Song, B., Wang, J., Yan, Z., Liu, Z., Pan, X., Zhang, Y. and Zhang, X., Microfluidics for the rapid detection of Staphylococcus aureus using antibody-coated microspheres. Bioengineered, 2020, 11(1), 1137–1145.
- Kim, Y. et al., Integrated microfluidic preconcentration and nucleic amplification system for detection of influenza A virus H1N1 in saliva. Micromachines (Basel), 2020, 11(2), 203.
- Ramachandran, A. et al., Electric field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2. Proc. Natl. Acad. Sci. USA, 2020, 117(47), 29518–29525.
Abstract Views: 368
PDF Views: 142