To 2D or 3D Cell Culture - That is no longer the question
2D vs 3D Cell Culture
Over the past few years, it has become evident that traditional 2D monolayer cell cultures often fail to accurately replicate the complex cellular microenvironment found in living organisms (1,2). In contrast, 3D cell-based assays allow cells to grow into three-dimensional structures that more closely mimic the architecture and interactions found in tissues and organs. This enables researchers to observe cellular behavior, such as cell-cell communication, migration, and differentiation, in a more physiologically relevant context (4).
The transition from 2D to 3D in vitro models is redefining efficacy and safety testing in drug discovery programs. By more accurately mimicking human tissue and organ responses, the 3D cell models provide more predictive information on how a drug will behave in vivo, as long as they are designed to answer a specific biological question. This means that the key to success of 3D cell culture lies in accurately defining the context of use and understanding the translatable value of each measured endpoint.
3D Cell Culture vs Industry-ready 3D Cell Culture
What sets the 3D in vitro models, which are ready for industrial application, apart from the rest of the available solutions? Before we delve deeper into the particular aspects, we need to address the importance of defining a specific biological question with a clear context of use, which we would like to answer by applying 3D in vitro models.
“Context of Use” - a little-known phrase but one that has profound implications. The Context of Use underscores the importance of considering the practical and real-world aspects of how an assay/test will be used or applied. This understanding helps guide decision-making, assessment, and optimization to ensure that products and processes are safe, effective, and fit for their intended purpose. Understanding the context of use has great implications across the drug discovery continuum that focusses on developing the right in vitro model to answer a specific biological question while maintaining the desired balance between physiological relevance and throughput. Adopting the right 3D in vitro model across the spectrum ensures that the same results can be reproduced, time and time again for meaningful data enabling early-stage decision-making. Industry-ready 3D in vitro models do just that. They create a model that is designed to answer a specific question in the drug discovery continuum and will deliver the same results consistently (3,5).
The 3 Critical Aspects of Industry-ready 3D Cell Culture
Scalability: The Competitive Edge
Many of the available 3D in vitro models are efficient at answering certain biological questions, however they struggle to scale up for automation or even high-throughput screening – a critical requirement in drug discovery and consistent data generation. 3D in vitro models, which are ready to be applied for industrial purposes, are not only sophisticated in terms of biological relevance but are also adaptable to large-scale applications. Their compatibility with high throughput automated systems makes them exceptionally suitable for screening vast compound libraries, the backbone of drug discovery and hit to lead optimization in pharma (2).
Reliability: Validated Results
Another challenge often faced when working with 3D cell culture models is maintaining the reliability of data generated by 3D in vitro models that have heterogenous cell sources, donors etc. Scalable models that are designed for a specific context of use are also meant to be reliable and not prone to certain variables that biology introduces into an assay. The reliability of a model is crucial especially for chronic disease studies and long-term drug effect assessments (2,5).
Reproducibility: The Cornerstone of Reliability
Reproducibility, enabled through high-quality, standardized production processes, is a cornerstone of scientific research. High reproducibility guarantees that each 3D in vitro model is produced with meticulous precision, ensuring consistency across batches. This uniformity is vital for comparative studies and large-scale screenings, where variability can skew results and impede the development of reliable therapeutics (2).
InSphero's Model of Excellence: Pioneering Scalable, Reliable and Reproducible 3D Cell Culture Models for Efficacy and Safety Testing
Scalability, reliability, and reproducibility are the mainstay of any decision making in therapeutic development, and the cornerstones of the 3D in vitro technology and solutions at InSphero.
What sets our 3D cell culture models apart is not just the high physiological relevance, but the ability to maintain high scalability, reliability, and reproducibility while answering a specific biological question.
InSphero's 3D in vitro models are versatile, finding applications across a range of therapeutic areas. They are particularly beneficial in fields like Toxicology, MASH, Diabetes, and Oncology, where the complex cellular microenvironment plays a crucial role in therapeutic response and resistance. Being able to maintain physiological complexity at scale makes InSphero’s solutions the only ones on market that can reliably answer complex biological questions and facilitate better decision making.
Next on the Blog
When it is clear that 3D Cell culture is the right method for addressing your biological question, there is a follow-up, even more relevant question you need to ask: “What is the right 3D in vitro system to use?”
For more on the difference between the different 3D in vitro cell-based systems, stay tuned for our next blog where we will delve into the relevant and fundamental differences between Spheroids, Organoids and Organ-on-chip models.
References
- Breslin, S., & O'Driscoll, L. (2013). Three-dimensional cell culture: the missing link in drug discovery. Drug Discovery Today, 18(5-6), 240-249.
- Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014). Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay and Drug Development Technologies, 12(4), 207-218.
- Langhans, S. A. (2018). Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning. Frontiers in Pharmacology, 9, 6.
- Knight, E., & Przyborski, S. (2015). Advances in 3D cell culture technologies enabling tissue-like structures to be created in vitro. Journal of Anatomy, 227(6), 746-756.
- 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.
- Horvath, P., Aulner, N., Bickle, M., Davies, A. M., Nery, E. D., Ebner, D., Montoya, M. C., Östling, P., Pietiäinen, V., Price, L. S., Shorte, S. L., Turcatti, G., von Schantz, C., & Carragher, N. O. (2016). Screening out irrelevant cell-based models of disease. Nature Reviews Drug Discovery, 15(11), 751-769.
