In the latter case, the ability to simulate the microtumor environment, communication between tumor cells, the effects of the tumor stroma environment, and the interaction of tumor cells with other surrounding cell types such as epithelial cells or fibroblasts, can enhance the ability to study mechanisms of tumorigenesis, cell migration and invasion, and metastasis.
One of the main and ongoing challenges has been to develop in vitro 3D cell culture systems that are compatible with industrial-scale applications and are readily automatable for high-throughput screening assays.
Jens Kelm, Ph.D., CSO and co-founder of InSphero, described three 3D cell culture methods that are currently most broadly accepted in the industry: cell constructs embedded in hydrogels; cells grown in scaffolds; and cellular self-assembly leading to spheroid formation. InSphero’s approach leads to the formation of scaffold-free 3D multicellular spheroids in a 96-well format. The company’s GravityPLUS™ technology automates the classic hanging drop methodology, in which cells in hanging drops of culture media descend and assemble into microtissue spheroids without the need for any support matrices or contact with any surfaces.
“We have exploited the versatility of hanging drop production by uncoupling the generation of microtissues from downstream applications,” said Dr. Kelm. “This was the creation of our platform, producing very uniform spheroids or microtissues while also allowing for compound treatments, microscopic analysis and assays, to get the best of both worlds!”
In his presentation at the SMi meeting, Dr. Kelm described the availability of an increasing variety of model systems available to industry and the research community for testing the safety, toxicity, and efficacy of drug compounds in in vitro systems and minimizing the need for animal testing. The demand for good in vitro model systems for screening extends beyond the pharmaceutical industry, with safety assessment of chemicals and other compounds important for the chemicals and cosmetics industries as well.
“We are using reporter systems that are allowing us to perform target validation in 3D model systems,” said Dr. Kelm. This has revealed sometimes substantial differences in the effects of drugs on microtissues versus cells grown in monolayer systems, and in particular in models of tumor growth and proliferation.
One goal going forward is standardization. It would be convenient, for example, to have standardized 3D liver and cardiac model systems available for safety testing. “It is important to generate comparable results, to test on the same model and be able to compare results over years and across drugs,” added Dr. Kelm.
Dr. Kelm foresees continued progress in mimicking interconnected, complex tissue constructs in functional living tissue models—so-called body-on-a-chip concepts. Two consortia, one in the United States and one in Europe, are working on this concept. InSphero is participating in the European project, in which the different tissue types are produced externally as 3D spherical constructs and then loaded onto a microchip, which is composed of interconnected compartments.
“There is consensus in the pharmaceutical industry that 3D model systems can provide a higher quality of information in vitro,” concluded Dr. Kelm.