Innovations in 3D culture are changing clinical and translational research. Laboratories and companies are increasingly using 3D models in drug discovery, and 3D cultures are contributing to the cutting edge of advanced therapeutics such as cell therapies.
In this article, we'll look at some examples of 3D culture innovations in drug discovery and cell therapy research. Then, we'll explore what's next for 3D aggregate cultures and how scientists and engineers are overcoming challenges in 3D.
An increasing number of companies and labs are taking advantage of the adaptability and scalability of 3D cell culture techniques. By implementing these models in both small-scale, advanced assays and high-throughput screens (HTS), researchers can significantly enhance the physiological relevance of their compound screening compared to traditional 2D cultures.
In the laboratory of Dr. Timothy Spicer at the Scripps Research Institute, scientists are taking this to new heights with an ultra-high-throughput 3D screening system based on Corning® 1536-well spheroid microplates. This system lets the lab test hundreds of thousands of compounds against melanoma and other cancers in 3D.
Single tools for 3D cell culture provide greater biological relevance, but by combining tools, researchers can create an advanced culture environment to conduct novel experiments in a familiar format. Researchers created a model of the blood-brain barrier (BBB)—a semipermeable barrier that controls which molecules and ions can cross into the brain—by culturing a monolayer of BBB cell types in Corning Transwell® inserts, then placing the inserts over 3D brain tissue grown in Corning spheroid plates. The model is helping pharmacology researchers predict the ability of drugs to penetrate the BBB, which is an important consideration in drug development. The model is also helping scientists understand how diseases alter BBB functioning.
3D aggregate culture techniques are also contributing to the development of investigational cell therapies, which involve transferring cultured or engineered cells into patients. For example, for certain cell types, injecting aggregates rather than suspensions of single cells can improve the survival of therapeutic cells after administration.
Whitney Cary Wilson, Field Application Scientist at Corning Life Sciences, explained the potential benefits of 3D formulations for cell therapies. "Cells themselves typically do not like to be alone. Suppose we're talking about injecting cell types that normally exist in tissues. In that case, they might prefer to be injected as an aggregate together, and they will survive better and have better engraftment long term in the patient," Wilson said. This can be particularly helpful in cases where the cell therapy should have a durable effect, such as in tissue reconstruction, she noted.
SymbioCellTech is developing one such example. This biotech firm is working on a treatment for Type 1 diabetes based on "neo-islets," 3D clusters of multiple cell types designed to replace the pancreatic islets that produce insulin in patients.
Another cell therapy company utilizing 3D technology is FibroBiologics, which is developing fibroblast-based, investigational therapies for multiple sclerosis, degenerative disc disease, and other conditions. FibroBiologics cultured fibroblast spheroids in Corning Elplasia® 12K flasks and featured them at the Corning 2024 3D Cell Culture Summit.
What's next for 3D aggregate cultures? We spoke with experts at Corning about trends they see in 3D culture. They explain challenges with 3D models that still need to be overcome and how Corning is developing tools and protocols to address these challenges.
Wilson predicts that standardized 3D assays will be "widely used by most drug discovery customers in the near future" due to the advantages these assays offer. 3D assays "provide additional important insight into how a therapeutic candidate may perform in vivo, saving companies time, money, and resources," she said.
Stéphanie Metzger, Scientific Support Specialist at Corning, added that 3D models can help drug developers "accelerate the timeline from initial drug or treatment discovery to clinical trials."
Mikael Garcia, Field Application Scientist for Corning EMEA, anticipates that 3D formulations of cell therapies will be increasingly used in the clinic, although this will take time. Wilson added, "I believe that 3D formulations of cell therapies will become more and more common to improve engraftment and efficacy of the therapeutic. If we create an environment that is more in vivo-like prior to administering the cellular therapeutic, the chances of engraftment and longer-term survival of the cell therapy itself will improve."
Current challenges include the need for standardized 3D protocols, as well as the need for improved techniques for imaging and characterizing 3D structures. "Standardization is an important challenge. There is a lot of heterogeneity in experimental designs, protocols, and validation criteria," Metzger said.
Wilson and Garcia noted that although some imaging techniques and tools are available for 3D, improved imaging solutions are still needed. "Customers would love to see a solution that can be used for imaging live spheroids without harming the ECM," Wilson said.
Garcia explained that the challenges in imaging and characterization stem from several factors. First, the life science field has more experience with imaging 2D compared with 3D structures. In addition, light cannot penetrate deeply into 3D structures, and 3D cultures are inherently more complex.
Wilson added, "In 2D cultures, typically you have more of a homogeneous population, and often in 3D cultures it's much more heterogeneous. So it can be difficult to understand exactly what types of markers should be expressed and what the specific locus within that organoid or structure is where those markers should be expressed." Although several tools are available to aid in complex analyses, further work is needed to integrate live imaging and analyses into 3D.
Corning Life Sciences continues to invest in customer-driven innovation by listening to common challenges and requests. Recently, Corning developed Elplasia flasks in response to customer needs for greater reproducibility and scalability of 3D techniques.
Catherine Siler, Field Application Scientist Manager at Corning, said that xeno-free and more defined ECMs are particularly important for laboratories developing therapeutic products. "As this type of work gets closer to the patient, it's more important to have something that's more defined or has fewer animal components. We've heard that call, so we're working on that," Siler said.
For companies that intend to develop clinical applications, Garcia emphasized the importance of closed systems and the ability to comply with Good Manufacturing Practices (GMP) standards. "What's complicated today is the regulations around the way to control the cells. If you want to go to patients, you need a closed system," Garcia said. Corning's work in developing closed systems and aseptic transfer solutions can help with these needs.
3D models in drug discovery and clinical research are complex. Advice and assistance from Corning's experts can help you find and optimize the best tools and models for your work.
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