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The importance of 3D cell culture in drug discovery and development

Yıl 2024, , 224 - 230, 30.12.2024
https://doi.org/10.51753/flsrt.1488871

Öz

Three-dimensional (3D) cell culture techniques represent a transformative advancement in biomedical research, particularly in drug discovery and development. By more closely replicating the physiological and microenvironmental conditions of in vivo tissues, 3D cell cultures enable more accurate assessments of drug efficacy, toxicity, and therapeutic potential compared to traditional two-dimensional (2D) cultures. These systems not only provide a more realistic model for preclinical testing but also allow for the study of complex cell-cell and cell-matrix interactions, which are often overlooked in 2D systems. This review provides a comprehensive examination of studies utilizing spheroids and organoids in 3D culture systems for drug screening and development. Furthermore, it highlights the critical role of these models in uncovering novel therapeutic targets, understanding disease mechanisms, and optimizing drug delivery strategies. Key challenges, such as scalability, standardization, and integration with high-throughput screening platforms, are also discussed. In conclusion, 3D cell culture techniques hold immense promise for revolutionizing the drug discovery pipeline, offering a more predictive and ethical approach to preclinical research while bridging the gap between laboratory findings and clinical outcomes.

Kaynakça

  • Achilli, T. M., Meyer, J., & Morgan, J. R. (2012). Advances in the formation, use and understanding of multi-cellular spheroids. Expert Opinion on Biological Therapy, 12(10), 1347.
  • Ajjarapu, S. M., Tiwari, A., & Kumar, S. (2023). Applications and utility of three-dimensional in vitro cell culture for therapeutics. Future Pharmacology, 3(1), 213-228.
  • Anton, D., Burckel, H., Josset, E., & Noel, G. (2015). Three-dimensional cell culture: a breakthrough in vivo. International Journal of Molecular Sciences, 16(3), 5517-5527.
  • Arrowsmith, J., & Miller, P. (2013). Phase II and phase III attrition rates 2011-2012. Nature Reviews Drug Discovery, 12(8), 569-570.
  • Ascheid, D., Baumann, M., Pinnecker, J., Friedrich, M., Szi-Marton, D., Medved, C., ... & Henke, E. (2024). A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy. Nature Communications, 15(1), 3599.
  • Baillargeon, P., Shumate, J., Hou, S., Fernandez-Vega, V., Marques, N., Souza, G., ... & Scampavia, L. (2019). Automating a magnetic 3D spheroid model technology for high-throughput screening. SLAS TECHNOLOGY: Translating Life Sciences Innovation, 24(4), 420-428.
  • Białkowska, K., Komorowski, P., Bryszewska, M., & Miłowska, K. (2020). Spheroids as a type of three-dimensional cell cultures—examples of methods of preparation and the most important application. International Journal of Molecular Sciences, 21(17), 6225.
  • Biju, T. S., Priya, V. V., & Francis, A. P. (2023). Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review. Drug Delivery and Translational Research, 13(9), 2239-2253.
  • Biju, T. S., Priya, V. V., & Francis, A. P. (2023). Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review. Drug Delivery and Translational Research, 13(9), 2239-2253.
  • Carvalho, M. P., Costa, E. C., & Correia, I. J. (2017). Assembly of breast cancer heterotypic spheroids on hyaluronic acid coated surfaces. Biotechnology Progress, 33(5), 1346-1357.
  • Carvalho, M. P., Costa, E. C., Miguel, S. P., & Correia, I. J. (2016). Tumor spheroid assembly on hyaluronic acid-based structures: A review. Carbohydrate Polymers, 150, 139-148.
  • Chaicharoenaudomrung, N., Kunhorm, P., & Noisa, P. (2019). Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling. World Journal of Stem Cells, 11(12), 1065.
  • Chueh, B. H., Zheng, Y., Torisawa, Y. S., Hsiao, A. Y., Ge, C., Hsiong, S., ... & Takayama, S. (2010). Patterning alginate hydrogels using light-directed release of caged calcium in a microfluidic device. Biomedical Microdevices, 12(1), 145-151.
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  • Cvetkovic, C., Raman, R., Chan, V., Williams, B. J., Tolish, M., Bajaj, P., ... & Bashir, R. (2014). Three-dimensionally printed biological machines powered by skeletal muscle. Proceedings of the National Academy of Sciences, 111(28), 10125-10130.
  • De Leo, V., Marras, E., Maurelli, A. M., Catucci, L., Milano, F., & Gariboldi, M. B. (2024). Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models. International Journal of Molecular Sciences, 25(6), 3392.
  • Demirel, G. (2021). Karaciğer hücreleri ve organoidlerin üç boyutlu kültürlerinde kullanılmak üzere geliştirilmiş biyomalzemeler. Frontiers in Life Sciences and Related Technologies, 2(3), 111-119.
  • Demirel, G. (2023). Morphological investigation of liver cancer cells in gelatin/alginate/hyaluronic acid scaffolds, Master's Thesis, Istanbul University, Council of Higher Education Thesis Center. pp. 1-76.
  • Demirel, G., Cakıl, Y. D., Koltuk, G., Aktas, R. G., & Calıskan, M. (2024). The use of hyaluronic acid in a 3D biomimetic scaffold supports spheroid formation and the culture of cancer stem cells. Scientific Reports, 14(1), 19560.
  • Di Cio, S., Marhuenda, E., Haddrick, M., & Gautrot, J. E. (2024). Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics. Scientific Reports, 14(1), 1-13.
  • Dobaño-López, C., Valero, J. G., Araujo-Ayala, F., Nadeu, F., Gava, F., Faria, C., ... & Pérez-Galán, P. (2024). Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target. Blood Cancer Journal, 14(1), 75.
  • Dutta, D., Heo, I., & Clevers, H. (2017). Disease modeling in stem cell-derived 3D organoid systems. Trends in Molecular Medicine, 23(5), 393-410.
  • Emond, R., Griffiths, J. I., Grolmusz, V. K., Nath, A., Chen, J., Medina, E. F., ... & Bild, A. H. (2023). Cell facilitation promotes growth and survival under drug pressure in breast cancer. Nature Communications, 14(1), 3851.
  • Fang, Y., & Eglen, R. M. (2017). Three-dimensional cell cultures in drug discovery and development. Slas discovery: Advancing Life Sciences R&D, 22(5), 456-472.
  • Fennema, E., Rivron, N., Rouwkema, J., van Blitterswijk, C., & De Boer, J. (2013). Spheroid culture as a tool for creating 3D complex tissues. Trends in Biotechnology, 31(2), 108-115.
  • Gu, B. K., Choi, D. J., Park, S. J., Kim, Y. J., & Kim, C. H. (2018). 3D bioprinting technologies for tissue engineering applications. Cutting-Edge Enabling Technologies for Regenerative Medicine, 15-28.
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  • Ingber, D. E., Mow, V. C., Butler, D., Niklason, L., Huard, J., Mao, J., ... & Vunjak-Novakovic, G. (2006). Tissue engineering and developmental biology: going biomimetic. Tissue Engineering, 12(12), 3265-3283.
  • Jayme, C. C., Pires, A. F., Fernandes, D. S., Bi, H., & Tedesco, A. C. (2022). DNA polymer films used as drug delivery systems to early-stage diagnose and treatment of breast cancer using 3D tumor spheroids as a model. Photodiagnosis and Photodynamic Therapy, 37, 102575.
  • Jordan, L. M. O., Vega, V. F., Shumate, J., Peles, A., Zeiger, J., Scampavia, L., & Spicer, T. P. (2024). Protocol for high throughput 3D drug screening of patient derived melanoma and renal cell carcinoma. SLAS Discovery, 29(3), 100141.
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The importance of 3D cell culture in drug discovery and development

Yıl 2024, , 224 - 230, 30.12.2024
https://doi.org/10.51753/flsrt.1488871

Öz

Three-dimensional (3D) cell culture techniques represent a transformative advancement in biomedical research, particularly in drug discovery and development. By more closely replicating the physiological and microenvironmental conditions of in vivo tissues, 3D cell cultures enable more accurate assessments of drug efficacy, toxicity, and therapeutic potential compared to traditional two-dimensional (2D) cultures. These systems not only provide a more realistic model for preclinical testing but also allow for the study of complex cell-cell and cell-matrix interactions, which are often overlooked in 2D systems. This review provides a comprehensive examination of studies utilizing spheroids and organoids in 3D culture systems for drug screening and development. Furthermore, it highlights the critical role of these models in uncovering novel therapeutic targets, understanding disease mechanisms, and optimizing drug delivery strategies. Key challenges, such as scalability, standardization, and integration with high-throughput screening platforms, are also discussed. In conclusion, 3D cell culture techniques hold immense promise for revolutionizing the drug discovery pipeline, offering a more predictive and ethical approach to preclinical research while bridging the gap between laboratory findings and clinical outcomes.

Kaynakça

  • Achilli, T. M., Meyer, J., & Morgan, J. R. (2012). Advances in the formation, use and understanding of multi-cellular spheroids. Expert Opinion on Biological Therapy, 12(10), 1347.
  • Ajjarapu, S. M., Tiwari, A., & Kumar, S. (2023). Applications and utility of three-dimensional in vitro cell culture for therapeutics. Future Pharmacology, 3(1), 213-228.
  • Anton, D., Burckel, H., Josset, E., & Noel, G. (2015). Three-dimensional cell culture: a breakthrough in vivo. International Journal of Molecular Sciences, 16(3), 5517-5527.
  • Arrowsmith, J., & Miller, P. (2013). Phase II and phase III attrition rates 2011-2012. Nature Reviews Drug Discovery, 12(8), 569-570.
  • Ascheid, D., Baumann, M., Pinnecker, J., Friedrich, M., Szi-Marton, D., Medved, C., ... & Henke, E. (2024). A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy. Nature Communications, 15(1), 3599.
  • Baillargeon, P., Shumate, J., Hou, S., Fernandez-Vega, V., Marques, N., Souza, G., ... & Scampavia, L. (2019). Automating a magnetic 3D spheroid model technology for high-throughput screening. SLAS TECHNOLOGY: Translating Life Sciences Innovation, 24(4), 420-428.
  • Białkowska, K., Komorowski, P., Bryszewska, M., & Miłowska, K. (2020). Spheroids as a type of three-dimensional cell cultures—examples of methods of preparation and the most important application. International Journal of Molecular Sciences, 21(17), 6225.
  • Biju, T. S., Priya, V. V., & Francis, A. P. (2023). Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review. Drug Delivery and Translational Research, 13(9), 2239-2253.
  • Biju, T. S., Priya, V. V., & Francis, A. P. (2023). Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review. Drug Delivery and Translational Research, 13(9), 2239-2253.
  • Carvalho, M. P., Costa, E. C., & Correia, I. J. (2017). Assembly of breast cancer heterotypic spheroids on hyaluronic acid coated surfaces. Biotechnology Progress, 33(5), 1346-1357.
  • Carvalho, M. P., Costa, E. C., Miguel, S. P., & Correia, I. J. (2016). Tumor spheroid assembly on hyaluronic acid-based structures: A review. Carbohydrate Polymers, 150, 139-148.
  • Chaicharoenaudomrung, N., Kunhorm, P., & Noisa, P. (2019). Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling. World Journal of Stem Cells, 11(12), 1065.
  • Chueh, B. H., Zheng, Y., Torisawa, Y. S., Hsiao, A. Y., Ge, C., Hsiong, S., ... & Takayama, S. (2010). Patterning alginate hydrogels using light-directed release of caged calcium in a microfluidic device. Biomedical Microdevices, 12(1), 145-151.
  • Costa, E. C., de Melo‐Diogo, D., Moreira, A. F., Carvalho, M. P., & Correia, I. J. (2018). Spheroids formation on non‐adhesive surfaces by liquid overlay technique: Considerations and practical approaches. Biotechnology Journal, 13(1), 1700417.
  • Cvetkovic, C., Raman, R., Chan, V., Williams, B. J., Tolish, M., Bajaj, P., ... & Bashir, R. (2014). Three-dimensionally printed biological machines powered by skeletal muscle. Proceedings of the National Academy of Sciences, 111(28), 10125-10130.
  • De Leo, V., Marras, E., Maurelli, A. M., Catucci, L., Milano, F., & Gariboldi, M. B. (2024). Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models. International Journal of Molecular Sciences, 25(6), 3392.
  • Demirel, G. (2021). Karaciğer hücreleri ve organoidlerin üç boyutlu kültürlerinde kullanılmak üzere geliştirilmiş biyomalzemeler. Frontiers in Life Sciences and Related Technologies, 2(3), 111-119.
  • Demirel, G. (2023). Morphological investigation of liver cancer cells in gelatin/alginate/hyaluronic acid scaffolds, Master's Thesis, Istanbul University, Council of Higher Education Thesis Center. pp. 1-76.
  • Demirel, G., Cakıl, Y. D., Koltuk, G., Aktas, R. G., & Calıskan, M. (2024). The use of hyaluronic acid in a 3D biomimetic scaffold supports spheroid formation and the culture of cancer stem cells. Scientific Reports, 14(1), 19560.
  • Di Cio, S., Marhuenda, E., Haddrick, M., & Gautrot, J. E. (2024). Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics. Scientific Reports, 14(1), 1-13.
  • Dobaño-López, C., Valero, J. G., Araujo-Ayala, F., Nadeu, F., Gava, F., Faria, C., ... & Pérez-Galán, P. (2024). Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target. Blood Cancer Journal, 14(1), 75.
  • Dutta, D., Heo, I., & Clevers, H. (2017). Disease modeling in stem cell-derived 3D organoid systems. Trends in Molecular Medicine, 23(5), 393-410.
  • Emond, R., Griffiths, J. I., Grolmusz, V. K., Nath, A., Chen, J., Medina, E. F., ... & Bild, A. H. (2023). Cell facilitation promotes growth and survival under drug pressure in breast cancer. Nature Communications, 14(1), 3851.
  • Fang, Y., & Eglen, R. M. (2017). Three-dimensional cell cultures in drug discovery and development. Slas discovery: Advancing Life Sciences R&D, 22(5), 456-472.
  • Fennema, E., Rivron, N., Rouwkema, J., van Blitterswijk, C., & De Boer, J. (2013). Spheroid culture as a tool for creating 3D complex tissues. Trends in Biotechnology, 31(2), 108-115.
  • Gu, B. K., Choi, D. J., Park, S. J., Kim, Y. J., & Kim, C. H. (2018). 3D bioprinting technologies for tissue engineering applications. Cutting-Edge Enabling Technologies for Regenerative Medicine, 15-28.
  • Handschel, J. G., Depprich, R. A., Kübler, N. R., Wiesmann, H. P., Ommerborn, M., & Meyer, U. (2007). Prospects of micromass culture technology in tissue engineering. Head & face medicine, 3, 1-4.
  • Ingber, D. E., Mow, V. C., Butler, D., Niklason, L., Huard, J., Mao, J., ... & Vunjak-Novakovic, G. (2006). Tissue engineering and developmental biology: going biomimetic. Tissue Engineering, 12(12), 3265-3283.
  • Jayme, C. C., Pires, A. F., Fernandes, D. S., Bi, H., & Tedesco, A. C. (2022). DNA polymer films used as drug delivery systems to early-stage diagnose and treatment of breast cancer using 3D tumor spheroids as a model. Photodiagnosis and Photodynamic Therapy, 37, 102575.
  • Jordan, L. M. O., Vega, V. F., Shumate, J., Peles, A., Zeiger, J., Scampavia, L., & Spicer, T. P. (2024). Protocol for high throughput 3D drug screening of patient derived melanoma and renal cell carcinoma. SLAS Discovery, 29(3), 100141.
  • Kahn-Krell, A., Pretorius, D., Ou, J., Fast, V. G., Litovsky, S., Berry, J., ... & Zhang, J. (2021). Bioreactor suspension culture: Differentiation and production of cardiomyocyte spheroids from human induced pluripotent stem cells. Frontiers in Bioengineering and Biotechnology, 9, 674260.
  • Kim, J. H., An, G. H., Kim, J. Y., Rasaei, R., Kim, W. J., Jin, X., Woo, D. H., Han, C., Yang, S. R., Kim, J. H., & Hong, S. H. (2021). Human pluripotent stem-cell-derived alveolar organoids for modeling pulmonary fibrosis and drug testing. Cell Death Discovery, 7(1). https://doi.org/10.1038/s41420-021-00439-7.
  • Knowlton, S., Onal, S., Yu, C. H., Zhao, J. J., & Tasoglu, S. (2015). Bioprinting for cancer research. Trends in Biotechnology, 33(9), 504–513. https://doi.org/10.1016/J.TIBTECH.2015.06.007.
  • Kong, J., Lee, H., Kim, D., Han, S. K., Ha, D., Shin, K., & Kim, S. (2020). Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients. Nature Communications, 11(1), 5485.
  • La-Beck, N. M., Liu, X., Shmeeda, H., Shudde, C., & Gabizon, A. A. (2021, January). Repurposing amino-bisphosphonates by liposome formulation for a new role in cancer treatment. In Seminars in Cancer Biology (Vol. 68, pp. 175-185). Academic Press.
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  • Lin, R. Z., & Chang, H. Y. (2008). Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnology Journal, 3(9-10), 1172-1184.
  • Liu, D., Chen, S., & Win Naing, M. (2021). A review of manufacturing capabilities of cell spheroid generation technologies and future development. Biotechnology and Bioengineering, 118(2), 542-554.
  • Lu, P., Weaver, V. M., & Werb, Z. (2012). The extracellular matrix: A dynamic niche in cancer progression. Journal of Cell Biology, 196(4), 395-406.
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Toplam 73 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sentetik Biyoloji, Yapısal Biyoloji , Doku Mühendisliği
Bölüm Derlemeler
Yazarlar

Gamze Demirel 0000-0002-5501-3736

Gürsel Koltuk 0000-0002-7330-1301

Yayımlanma Tarihi 30 Aralık 2024
Gönderilme Tarihi 23 Mayıs 2024
Kabul Tarihi 19 Aralık 2024
Yayımlandığı Sayı Yıl 2024

Kaynak Göster

APA Demirel, G., & Koltuk, G. (2024). The importance of 3D cell culture in drug discovery and development. Frontiers in Life Sciences and Related Technologies, 5(3), 224-230. https://doi.org/10.51753/flsrt.1488871

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