Authored by The Scripps Research Institute in Florida, in collaboration with Cold Spring Harbor Laboratory, Greiner Bio-One, Nano3D Biosciences, Inc., University of Texas Health Science Center at Houston, and the Dana-Farber Cancer Institute, the article depicts results obtained utilizing Magnetic 3D Cell Culture technology to generate ex vivo pancreatic tumor models for high throughput drug screening (HTS).
With the ever increasing cost of drug development, there is high demand for novel approaches to efficiently discover new drugs. Traditionally, drug discovery uses either animal models or 2D cell culture to screen drugs, whose selection requires a tradeoff between accuracy and scale. 3D cell culture, like magnetic 3D cell culture (m3D), is breaking the paradigm for in vitro methods to provide the predictiveness and accuracy comparable to in vivo models with the high-throughput productivity of 2D cell culture.
For this magnetic 3D assay, standard flat bottom 384 and 1536 well plates featuring a cell repellent surface were employed, combined with a magnetic 3D bioprinting technology. The homogeneous HTS organoid-based assay was standardized using well known anti-cancer agents against four patient-derived pancreatic cancer KRAS mutant associated primary cell lines, including cancer associated fibroblasts. This technology was further validated for its compatibility with HTS instrumentation and robotics by completing a cytotoxicity screen with a library of 3300 approved drugs. To determine the validity of 3D vs 2D HTS, a parallel screen was performed on the same cells in monolayer culture. These results indicate that an ex vivo clinically relevant 3D tumor model can be rapidly adapted and used for large scale drug screening, taking us one step closer to applying precision medicine to the treatment of cancer.
n3D President and CSO Glauco Souza said, “It is exciting that we picked the ‘needle in a haystack.’ We identified, out of the 3,300 approved drugs, the compound that is currently undergoing Phase I clinical trials for the treatment of pancreatic cancer, disulfiram. Disulfiram was only active in certain cancer specific 3D cultures, not in 2D.”
In this work, magnetic 3D bioprinting provided a strategic advantage, since it is a rapid, relatively easy, and reproducible method to print 3D cultures in high throughput. First author and Postdoctoral Fellow at The Scripps Research Institute Shurong Hou said, “These results further support the improved predictive value of 3D cell culture over 2D”.
“This work demonstrates a faster and more physiologically relevant cost-efficient drug discovery process, which ultimately will aid in avoiding possible false positives and improving the accuracy” said Timothy Spicer and Louis Scampavia, leaders of this project from The Scripps Research Institute.
For information on Magnetic 3D Cell Culture, contact Greiner Bio-One.
Greiner Bio-One North America, Inc. is a privately held plastic manufacturing company located in Monroe, NC whose three divisions manufacture a variety of products for the medical and research fields. The manufactured products include plasticware for the cultivation and analysis of cell and tissue cultures, microplates for high-throughput screening related to drug screening, products for blood and specimen collection, tests for the detection of bacteria and viruses, as well as, custom-made products. As an international manufacturer with global reach, Greiner Bio-One provides the manufacturing, distribution logistics and product application support to the world’s largest hospitals, pharmaceutical and biotechnology corporations.
For more information about Greiner Bio-One North America, Inc. please visit www.gbo.com.
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R33CA206949. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.